ArticleLiterature Review

Exercise-induced cardioprotection against myocardial ischemia-reperfusion injury

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Abstract

Myocardial ischemia-reperfusion (IR) injury is a major contributor to the morbidity and mortality associated with coronary artery disease. Muscular exercise is a countermeasure to protect against IR-induced cardiac injury in both young and old animals. Specifically, regular bouts of endurance exercise protect the heart against all levels of IR-induced injury. Proposed mechanisms to explain the cardioprotective effects of exercise include alterations in coronary circulation, expression of endoplasmic reticulum stress proteins, increased cyclooxygenase-2 activity, induction of myocardial heat shock proteins, improved cardiac antioxidant capacity, and/or elevation of ATP-sensitive potassium channels on both the sarcolemmal and the mitochondrial inner membranes. Moreover, it seems possible that other, yet to be defined, mechanisms of exercise-induced cardioprotection may also exist. Of the known putative cardioprotective mechanisms, current evidence suggests that elevated myocardial levels of antioxidants and increased expression of sarcolemmal ATP-sensitive potassium channels are both contributors to exercise-induced cardioprotection against IR injury. At present, it is unclear if these two protective mediators act independently or interact to contribute to exercise-induced cardioprotection. Understanding the molecular basis for exercise-induced cardioprotection will provide the required knowledge base to develop therapeutic approaches to protect the heart during an IR insult.

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... Continuing research is aimed to explore the therapeutic interventions against IR injury. Although numerous pharmacological and preconditioning approaches to cardioprotection have been explored, regular exercise participation is recognized as an important, cost-effective, and safer lifestyle intervention in the prevention and treatment of IR injury (10)(11)(12)(13)(14). Redundant protective effects are evident in the exercised heart, namely, increased levels of heat shock proteins (15), altered nitric oxide (NO) signaling (16)(17)(18), enhanced Ca 2+ handling proteins (19), improved ATP-sensitive potassium channels (20), and enhanced endogenous antioxidant (13,21). ...
... Continuing research is aimed to explore the therapeutic interventions against IR injury. Although numerous pharmacological and preconditioning approaches to cardioprotection have been explored, regular exercise participation is recognized as an important, cost-effective, and safer lifestyle intervention in the prevention and treatment of IR injury (10)(11)(12)(13)(14). Redundant protective effects are evident in the exercised heart, namely, increased levels of heat shock proteins (15), altered nitric oxide (NO) signaling (16)(17)(18), enhanced Ca 2+ handling proteins (19), improved ATP-sensitive potassium channels (20), and enhanced endogenous antioxidant (13,21). ...
... The proposed mechanisms underlying exercise-induced cardioprotection in IR are numerous. Some are systemic (12), some are vascular (12)(13)(14)21), some are neural (38,39), some are structural (9), and some are energetic/metabolic (40,41) including expression of selected mitochondrial proteins resulting in a mitochondrial phenotype that is resistant to IR-induced injury (13,19). While these studies generally support exerciseinduced adaptations that produce resistance to injury, few address the mitochondrial functional consequences following an injury. ...
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Rationale: Regular active exercise is considered therapeutic for cardiovascular disease, in part by increasing mitochondrial respiratory capacity, but a significant amount of exercise capacity is determined genetically. Animal models, demonstrating either high capacity aerobic running (HCR) or low capacity aerobic running (LCR) phenotypes, have been developed to study the intrinsic contribution, with HCR rats subsequently characterized as “disease resistant” and the LCRs as “disease prone.” Enhanced cardioprotection in HCRs has been variable and mutifactoral, but likely includes a metabolic component. These studies were conducted to determine the influence of intrinsic aerobic phenotype on cardiac mitochondrial function before and after ischemia and reperfusion. Methods: A total of 34 HCR and LCR rats were obtained from the parent colony at the University of Toledo, housed under sedentary conditions, and fed normal chow. LCR and HCR animals were randomly assigned to either control or ischemia-reperfusion (IR). On each study day, one HCR/LCR pair was anesthetized, and hearts were rapidly excised. In IR animals, the hearts were immediately flushed with iced hyperkalemic, hyperosmotic, cardioplegia solution, and subjected to global hypothermic ischemic arrest (80 min). Following the arrest, the hearts underwent warm reperfusion (120 min) using a Langendorff perfusion system. Following reperfusion, the heart was weighed and the left ventricle (LV) was isolated. A midventricular ring was obtained to estimate infarction size [triphenyltetrazolium chloride (TTC)] and part of the remaining tissue (~150 mg) was transferred to a homogenation buffer on ice. Isolated mitochondria (MITO) samples were prepared and used to determine respiratory capacity under different metabolic conditions. In control animals, MITO were obtained and prepared similarly immediately following anesthesia and heart removal, but without IR. Results: In the control rats, both resting and maximally stimulated respiratory rates were higher (32 and 40%, respectively; p < 0.05) in HCR mitochondria compared to LCR. After IR, resting MITO respiratory rates were decreased to about 10% of control in both strains, and the augmented capacity in HCRs was absent. Maximally stimulated rates also were decreased more than 50% from control and were no longer different between phenotypes. Ca++ retention capacity and infarct size were not significantly different between HCR and LCR (49.2 ± 5.6 vs. 53.7 ± 4.9%), nor was average coronary flow during reperfusion or arrhythmogenesis. There was a significant loss of mitochondria following IR, which was coupled with decreased function in the remaining mitochondria in both strains. Conclusion: Cardiac mitochondrial capacity from HCR was significantly higher than LCR in the controls under each condition. After IR insult, the cardiac mitochondrial respiratory rates were similar between phenotypes, as was Ca++ retention capacity, infarct size, and arrhythmogenicity, despite the increased mitochondrial capacity in the HCRs before ischemia. Relatively, the loss of respiratory capacity was actually greater in HCR than LCR. These data could suggest limits in the extent to which the HCR phenotype might be “protective” against acute tissue stressors. The extent to which any of these deficits could be “rescued” by adding an active exercise component to the intrinsic phenotype is unknown.
... However, when the heart is regularly exposed to mild IR without cell death (such as conditions caused by exercise training), it leads to augment cardioprotection through the preconditioning process [4,5]. In this regard, numerous studies show that regular exercise, even short-term of exercise training (1, 3 and 5 sessions) [4,[6][7][8][9], is one of the practical approaches of preconditioning to achieve cardioprotection and reduce the risk of IR-induced injury and death [4,10]. However, despite the recognition of some effective mechanisms of Exercise-induced cardioprotection, the cellular and molecular mechanisms that induce this adaptation remain as a complex and debated issue [3]. ...
... Comparing these two exercise training protocols (HIIT and MICT) can play an important role in identifying a more effective training program on cardioprotection. The mechanisms responsible for cardioprotection following exercise training remains a debated issue because of numerous affecting factors, including an increase in antioxidant capacity and levels of HPSs, alteration in glycolytic flux and nitric oxide (NO) signaling, improvement of ATP-dependent potassium channel function, augmentation of myocardial COX-2 activity, elevation of endoplasmic reticulum (ER) stress proteins, and changes in mitochondrial phenotype [3,8,[10][11][12]. In sum, despite some known cellular and molecular mechanisms in exercise-induced cardioprotection, all mechanisms responsible for cardiovascular adaptations and increased cardioprotection following exercise training, especially HIIT, are largely unknown and more research is needed to identify these mechanisms. ...
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Background Myocardial ischemia-reperfusion (IR) injury is a leading cause of death all over the world, so developing practical approaches to promote cardioprotection against IR injury is essential. Exercise training is an effective strategy to improve cardioprotection. Hence, the purpose of this study was to investigate the effect of short-term preconditioning with two types of high-intensity interval training (HIIT) and moderate intensity continuous training (MICT) on klotho and TRPC6 mechanisms in cardioprotection. Methods Eighty Male Wistar rats (250–300 g) were randomly divided into 7 groups, including Control, HIIT, MICT, Sham, IR, HIIT+IR, and MICT+IR. Training was performed in 5 consecutive days. HIIT protocol consisted of running on the treadmill at intervals 85–90% vo2max that separated by slow intensity periods at 50–60% vo2max. MICT program was performed at 70% VO2max at the same running distance with HIIT groups. The cardiac IR injury was induced by LAD occlusion followed by reperfusion. ELISA kit was used in order to measure the plasma levels of klotho, LDH and CK-MB, and TRPC6 expression was determined using the western blot technique. Data were analyzed using one way ANOVA and Tukey’s post hoc tests. Results The results of this study showed that both types of exercise training programs significantly increase plasma levels of klotho and reduce the infarct size and heart injury. In addition, the exercise training decreased the amount of TRPC6 channels expression during IR. However, the effect of HIIT on increasing the klotho and cardioprotection was greater compared to MICT. Conclusions Based on the results, even a short-term of aerobic exercise training, especially HIIT, promotes cardioprotection against IR injury and decreases infarct size via an increase in klotho and attenuate of protein expression of myocardial TRPC6 during IR.
... Regular exercise has been considered an effective method to improve heart function and reduce mortality of CVD. Several animal models and human epidemiological studies support the cardio-protective effect of exercise [4][5][6]. Several protective mechanisms demonstrated that exercise increased VO 2max (maximal oxygen consumption), improved cardiorespiratory fitness (CRF) [7], lipid profile [8], endothelial function [9], increased number of capillaries [10], and mitochondria anti-oxidant activity in the cardiovascular system [11]. However, while exercise typically results if beneficial effects on heart function, there are occasions when it could result in unexpected death during exercise especially for the CVD cohort [12][13][14]. ...
... In order to provide effective life style intervention to avoid the risk of CVD, exercise animal models were introduced to demonstrate safety and evaluate the clinical efficiency of exercise training (EX) [6,[15][16][17]. We researched both animal models and a publication which proved that exercise reduces the incidence of myocardial ischemia (MI), ischemia/reperfusion (I/R) injury, and atherosclerosis [18]. ...
Article
Cardiovascular disease (CVD) is a major global cause of mortality, which has prompted numerous studies seeking to reduce the risk of heart failure and sudden cardiac death. While regular physical activity is known to improve CVD associated morbidity and mortality, the optimal duration, frequency, and intensity of exercise remains unclear. To address this uncertainty, various animal models have been used to study the cardioprotective effects of exercise and related molecular mechanism such as the mice training models significantly decrease size of myocardial infarct by affecting Kir6.1, VSMC sarc-K ATP channels, and pulmonary eNOS. Although these findings cement the importance of animal models in studying exercise induced cardioprotection, the vast assortment of exercise protocols makes comparison across studies difficult. To address this issue, we review and break down the existent exercise models into categories based on exercise modality, intensity, frequency, and duration. The timing of sample collection is also compared and sorted into four distinct phases: pre-exercise (Phase I), mid-exercise (Phase II), exercise recovery (Phase III), and post-exercise (Phase IV). Finally, because the life-span of animals so are limited, small changes in animal exercise duration can corresponded to untenable amounts of human exercise. To address this limitation, we introduce the Life-Span Relative Exercise Time (RET life span ) as a method of accurately defining short-term, medium-term and long-term exercise relative to the animal’s life expectancy. Systematic organization of existent protocols and this new system of defining exercise duration will allow for a more solid framework from which researchers can extrapolate animal model data to clinical application.
... Many strategies have been considered to prevent cardiovascular diseases. However, despite a large amount of research on cardiovascular protective mechanisms, exercise is one of the most practical and effective preventive treatments, as Powers et al. [41] have ...
... Many strategies have been considered to prevent cardiovascular diseases. However, despite a large amount of research on cardiovascular protective mechanisms, exercise is one of the most practical and effective preventive treatments, as Powers et al. [41] have shown. We hypothesized that exercise regulates phenotype switching in VSMCs via the modulation of the Akt and MAKP signaling pathways. ...
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The mechanisms regulating vascular smooth muscle cell (VSMC) phenotype switching and the critical signal modulation affecting the VSMCs remain controversial. Physical exercise acts as an effective drug in preventing elevated blood pressure and improving vascular function. This study was designed to explore the influence of aerobic exercise on the suppression of VSMC phenotype switching by balancing of the Akt, also known as PKB (protein kinase B) and mitogen-activated protein kinase (MAPK) signaling pathways. Spontaneously hypertensive rats (SHRs) and normotensive rats were subjected to exercise treatment before measuring the vascular morphological and structural performances. Exercise induced reverse expression of VSMC protein markers (α-SM-actin, calponin, and osteopontin (OPN)) in spontaneously hypertensive rats. It is noteworthy that the low expression of phosphorylated Akt significantly decreased the expression of VSMC contractile phenotype markers (α-SM-actin and calponin) and increased the expression of the VSMC synthetic phenotype marker (OPN). However, the MAPK signal pathway exerts an opposite effect. VSMCs and whole vessels were treated by inhibitors, namely the p-Akt inhibitor, p-ERK inhibitor, and p-p38 MAPK inhibitors. VSMC phenotype markers were reversed. It is important to note that a significant reverse regulatory relationship was observed between the expression levels of MAPK and the contractile markers in both normotensive and spontaneously hypertensive rats. We demonstrate that aerobic exercise regulates the VSMC phenotype switching by balancing the Akt and MAPK signaling pathways in SHRs.
... Another major consequence of aging is increased oxidative stress and chronic inflammation, which are major causes of tissue damages and hence induction of apoptosis, particularly in heart tissues, which works continuously and is more susceptible to oxidative stress and inflammation-induced damages [32]. Increased oxidative stress is demonstrated to induce the expression of stress sensors such as HSPs particularly HSP-70, an activating factor of cell protection signaling pathways [26]. HSP-70 is also involved in the suppression of apoptosis, hence promotion of heart survival [26,43]. ...
... Increased oxidative stress is demonstrated to induce the expression of stress sensors such as HSPs particularly HSP-70, an activating factor of cell protection signaling pathways [26]. HSP-70 is also involved in the suppression of apoptosis, hence promotion of heart survival [26,43]. ...
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Aging-induced progressive decline of molecular and metabolic factors in the myocardium is suggested to be related with heart dysfunction and cardiovascular disease. Therefore, we evaluated the effects of exercise training and l-arginine supplementation on oxidative stress, inflammation, and apoptosis in ventricle of the aging rat heart. Twenty-four 24-month-aged Wistar rats were randomly divided into four groups: the aged control, aged exercise, aged l-arginine (orally administered with 150 mg/kg for 12 weeks), and aged exercise + l-arginine groups. Six 4-month-old rats were also considered the young control. Animals with training program performed exercise on a treadmill 5 days/week for 12 weeks. After 12 weeks, protein levels of Bax, Bcl-2, pro-caspase-3/cleaved caspase-3, cytochrome C, and heat shock protein (HSP)-70 were assessed. Tissue contents of total anti-oxidant capacity, superoxide dismutase, catalase, and levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 were analyzed. Histological and fibrotic changes were also evaluated. Treadmill exercise and l-arginine supplementation significantly alleviated aging-induced apoptosis with enhancing HSP-70 expression, increasing anti-oxidant enzyme activity, and suppressing inflammatory markers in the cardiac myocytes. Potent attenuation in apoptosis, inflammation, and oxidative stress was indicated in the rats with the combination of l-arginine supplementation and exercise program in comparison with each group (p < 0.05). In addition, fibrosis percentage and collagen accumulation were significantly lower in the rats with the combination treatment of l-arginine and exercise (p < 0.05). Treadmill exercise and l-arginine supplementation provided protection against age-induced increase in the myocyte loss and formation of fibrosis in the ventricle through potent suppression of oxidative stress, inflammations, and apoptosis pathways.
... Epidemiologic evidence shows that there is a strong relationship between people who are training regularly and are saved from cardiac infarction [36]. Regular exercise seems to be one of the best and most effective practical and tolerable approaches to heart protection [37]. Studies in this eld showed that in various physiological conditions such as exercise and altitudes-related ischemia, and also pathological conditions (such as diseases), the concentration of SDF and other stem factors such as CSF-G, SCF, C-KIT, SCa-1 are changed [38,39]. ...
... Several studies have reported that exercise training protects against cardiac MI in animal models Induces [73,74,75,76,77]. It seems to Regular training periods one of the best and most effective and tolerant approaches that cause cardiac protection [37]. Anatomical and physiological changes in the coronary arteries, head shock protein (HSPS), increased activity of cyclooxygenase-2 (COX-2), increased endoplasmic endothelial stress (ER), enhanced potassium function of ATP-dependent sarcolemma (sarcoKATP), increased levels of ATP-dependent potassium channels in mitochondria (mitoKATP), nitric oxide (NO), and increased the antioxidant capacity of the myocardium are among the cellular-molecular mechanisms involved in cardiac protection from cardiovascular injuries [76,78]. ...
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Background: One of the best and most effective applied and tolerable approaches for cardioprotecion is the regular exercise. In situation of exercise activity and even cardiac ischemic injury, the activity of the myocardial stem cells and their recruiting factors are changed so that contribute the adaptation and repairment of the myocardium. The aim of this study was to investigate the effect of myocardial preconditioning with high intensive interval training on SDF-1a myocardial levels, CXCR4 receptors and c-kit after acute myocardial infarction in male rats. Methods: 20 male Wistar rats (8 week old ,weight 234.8 ± 5.7 g) were randomly divided into 4 groups of control (C), training (T), myocardial infraction (MI) and training+ myocardial infraction (T+MI). The training groups performed two weeks of high intensity interval training in four sections. Each section included two or three days of practice sessions and two sessions each per a day. The number or intensity of the intervals increased in each section. SDF-1, CXCR4 and C-Kit proteins were measured by the Western blot method in the myocardial tissue and myocardial injury enzymes (CK, LDH, troponin T) were measured in serum. Results: The results of this study showed that that SDF-1, CXCR4 and C-Kit had a significant increase after two weeks of high intensity interval training and myocardial infraction. Also, serum enzyme measurements showed a positive effect of exercise, so that in the myocardium injury enzymes significantly increased in the myocardial infarction group compared with the other three groups, training and training- myocardial infarction (P<0.001). As well as, there was a significant difference between the groups of training -myocardial infarction in all of the enzymes of the myocardium injury compared to the control and training groups. Conclusions: Even short terms of high intensity interval training can increase the levels of proteins SDF1-a, CXCR4 and C-Kit in order to cardioprotection against myocardial injury through recruitment stem cells.
... 38 Numerous studies have provided evidence supporting that exercise training is an effective intervention which reduces myocardial I/R injury. [39][40][41] The protective effect of exercise against I/R injury was shown to be closely related to exercise-enhanced myocardial antioxidant capacity. 39 In fact, exercise was shown to reduce the infarct size after myocardial I/R injury, an effect which was abolished by suppressing SOD2. ...
... [39][40][41] The protective effect of exercise against I/R injury was shown to be closely related to exercise-enhanced myocardial antioxidant capacity. 39 In fact, exercise was shown to reduce the infarct size after myocardial I/R injury, an effect which was abolished by suppressing SOD2. 40,41 In the early phase after I/R injury, ROS production was markedly lower in the hearts of exercised mice than sedentary mice. ...
Article
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Exercise training has been widely recognized as a healthy lifestyle as well as an effective non-drug therapeutic strategy for cardiovascular diseases (CVD). Functional and mechanistic studies that employ animal exercise models as well as observational and interventional cohort studies with human participants, have contributed considerably in delineating the essential signaling pathways by which exercise promotes cardiovascular fitness and health. First, this review summarizes the beneficial impact of exercise on multiple aspects of cardiovascular health. We then discuss in detail the signaling pathways mediating exercise’s benefits for cardiovascular health. The exercise-regulated signaling cascades have been shown to confer myocardial protection and drive systemic adaptations. The signaling molecules that are necessary for exercise-induced physiological cardiac hypertrophy have the potential to attenuate myocardial injury and reverse cardiac remodeling. Exercise-regulated noncoding RNAs and their associated signaling pathways are also discussed in detail for their roles and mechanisms in exercise-induced cardioprotective effects. Moreover, we address the exercise-mediated signaling pathways and molecules that can serve as potential therapeutic targets ranging from pharmacological approaches to gene therapies in CVD. We also discuss multiple factors that influence exercise’s effect and highlight the importance and need for further investigations regarding the exercise-regulated molecules as therapeutic targets and biomarkers for CVD as well as the cross talk between the heart and other tissues or organs during exercise. We conclude that a deep understanding of the signaling pathways involved in exercise’s benefits for cardiovascular health will undoubtedly contribute to the identification and development of novel therapeutic targets and strategies for CVD.
... Previous studies show that intrinsic pathways that mediate cardiac adaptive responses to exercise are triggered rapidly, even after just 1-3 bouts of consecutive exercise, and are sufficiently robust to provide significant cardioprotection (Demirel et al., 2001;Powers et al., 2008). Among the candidate pathways involved in the adaptive response to acute exercise are those that maintain a balance between reactive oxygen species (ROS) and endogenous antioxidant defences. ...
Article
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Regular exercise has widespread health benefits. Fundamental to these beneficial effects is the ability of the heart to intermittently and substantially increase its performance without incurring damage, but the underlying homeostatic mechanisms are unclear. We identify the ROS-generating NADPH oxidase-4 (Nox4) as an essential regulator of exercise performance in mice. Myocardial Nox4 levels increase during acute exercise and trigger activation of the transcription factor Nrf2, with the induction of multiple endogenous antioxidants. Cardiomyocyte-specific Nox4-deficient (csNox4KO) mice display a loss of exercise-induced Nrf2 activation, cardiac oxidative stress and reduced exercise performance. Cardiomyocyte-specific Nrf2-deficient (csNrf2KO) mice exhibit similar compromised exercise capacity, with mitochondrial and cardiac dysfunction. Supplementation with an Nrf2 activator or a mitochondria-targeted antioxidant effectively restores cardiac performance and exercise capacity in csNox4KO and csNrf2KO mice respectively. The Nox4/Nrf2 axis therefore drives a hormetic response that is required for optimal cardiac mitochondrial and contractile function during physiological exercise.
... Therefore, the relaxation response to diazoxide (a K ATP channel activator) increases significantly, and the vasoconstriction response to glibenclamide (a K ATP channel inhibitor) becomes markedly suppressed [44,45]. As a result, upregulated protein expression of Kir6.1 after exercise shortens myocardial tissue oxygenation recovery time and protects the heart against I/R injury [58]. ...
Article
Myogenic contraction of vascular smooth muscle cells (VSMCs) in resistance arteries and arterioles plays a critical role in regulating peripheral resistance. Ion channels expressed in VSMCs control ion influx or efflux from the plasma membrane and endoplasmic reticulum to regulate membrane potential, which contributes to the regulation of vascular tone. With the depolarization of VSMC membranes, an elevation of intracellular calcium ion (Ca²⁺) concentration is mediated by voltage-gated Ca²⁺ channels and can trigger a vasoconstrictive response. In addition, potassium ion (K⁺) efflux through K⁺ channels can hyperpolarize VSMCs, resulting in vasodilation. However, in the pathophysiological progression of diseases such as hypertension, VSMCs undergo a wide range of pathological changes, among them is “electrical remodeling”, which refers to changes in ion channels. Under physiological or pathological conditions, exercise has a profound impact on the human body, and ion channels are an essential target of the beneficial adaptive responses. This review provides insight on the physiological function of ion channels in VSMCs, including CaV1.2 channels, voltage-gated K⁺ channels, large-conductance Ca²⁺-activated K⁺ channels, and inward-rectifier K⁺ channels, and the changes of these ion channels during hypertension. Focus is given to the effects of exercise on these ion channels and its implications in disease treatment.
... There are several examples of this in our profession. [2][3][4][5][6] There are also many physical therapists around the world actively engaged in these areas of research, and some are international leaders in their respective fields of basic science and applied physiology. [2][3][4][7][8][9][10][11][12][13][14][15][16][17] Despite the efforts of these research leaders, many in our profession continue to hold these views toward basic and applied physiological research. ...
... 110 However, the proposed strategies as of yet have not been proven to be "effective" in attenuating lethal IR injury and infarct size. Nonetheless, exercise has been shown increase the expression of endogenous antioxidants such as SOD1 and SOD2 in the mitochondria 111,112 possibly via activation of the transcription factor nuclear factor erythroid-2 (Nrf2). 113 In addition, exercise training has also been suggested to increase the activity of glutathione reductase in the heart via posttranslational modifications. ...
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Similar to ischemic preconditioning, high-intensity exercise has been shown to decrease infarct size following myocardial infarction. In this article, we review the literature on beneficial effects of exercise, exercise requirements for cardioprotection, common methods utilized in laboratories to study this phenomenon, and discuss possible mechanisms for exercise-mediated cardioprotection.
... These substances are important because they increase the safety and quality of food that is consumed and protect from the action of oxidizing substances that can cause diseases. [16][17][18] Several interrelated factors such as the decrease in the cellular ATP levels and the production of both reactive oxygen species (ROS) and reactive nitrogen species contribute to damage aer myocardial ischemia and reperfusion (I/R), 19 which is the leading cause of morbidity and mortality associated with cardiovascular diseases, a global public health problem. 16,20,21 Thus, antioxidants may be able to help overcome this situation. ...
Article
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Polyhydroquinolines (PHQs) are the unsymmetrical Hantzsch derivatives of 1,4-dihydropyridines with several biological applications. In this work, new fatty 2- and 3-substituted PHQ derivatives from different fatty acids and fatty alcohol feedstocks were synthesized at good yields via a four-component reaction (4CR). The antioxidant activities of fatty PHQs were investigated using three different antioxidant methods. The experiments showed that the compounds derived from 2-nitrobenzaldehyde and fatty palmitic (C16:0) and oleic (C18:1) chains showed better antioxidant activity. This revealed that combining the ortho NO2 group in the aromatic ring with the insertion of fatty chains in the PHQ core contributed to the antioxidant activity. However, among all the fatty PHQs tested, the fatty 2-substituted compound derived from oleyl alcohol and 2-nitrobenzaldehyde showed the highest antioxidant activity (EC50, 2.11-4.69 μM), which was similar to those of the antioxidant standards butylated hydroxytoluene (EC50, 1.98-6.47 μM) and vitamin E (EC50, 1.19-5.88 μM). In addition, this lipophilic compound showed higher antioxidant activity than the antihypertensive drug nifedipine (EC50, 49.25-126.86 μM). These results indicate that the new fatty PHQs may find novel applications as antioxidant additives.
... Sport is considered to have a positive effect on physical well-being (Amlani and Munir, 2014). Regular physical training is determined to be cardio-protective and preventative against a variety of chronic diseases (Bassuk and Manson, 2005;Powers et al., 2008;Rengo et al., 2013). Additionally, regular physical training has beneficial effects on metabolic syndrome by decreasing the adverse effects of its multifactorial and progressive pathogenesis (Church, 2011). ...
Article
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Sport is known to have many positive effects on mental and physical health. High-intensity exercise is considered to decrease muscle strength and induce muscle fatigue, which is associated with a higher risk of injury. In recreational alpine skiers, a decrease of eccentric peak hamstring torque, as an indication of muscle fatigue, occurs even after 1 day of skiing. The popularity of ski mountaineering is increasing enormously, but no studies are available on its effects on muscle strength. Therefore, the present study examined the consequences of ski mountaineering on muscle fatigue of the concentric/eccentric quadriceps and/or hamstrings. In addition, a possible role of myofascial foam rolling in reducing muscle fatigue was evaluated. Fifty recreational ski mountaineers (27 males, 23 females) completed five consecutive tours of ski mountaineering within 1 week. After each day of skiing, participants underwent an isokinetic muscle test assessing the concentric and eccentric muscle strength of both thighs. One group completed an additional session of myofascial foam rolling. Right and left concentric quadriceps peak torque, left hamstrings peak torque, left eccentric quadriceps peak torque, as well as right and left hamstring peak torque, were reduced after a single day of ski mountaineering (p ≤ 0.016 for all). However, no cumulative muscle fatigue was detected and we could not demonstrate any effect of myofascial foam rolling. The results show conclusively that a single day of ski mountaineering leads to a significant decrease of concentric and eccentric quadriceps and hamstring strength. Therefore, in order to improve muscle strength for the ski mountaineering season, a physical training program including concentric and eccentric methods can be recommended.
... [16] Moreover, exercise can lead to expression of selected mitochondrial proteins, resulting in a mitochondrial phenotype that is resistant to IR-induced damage. [17,18] Although numerous pharmacological and preconditioning approaches to cardioprotection have been explored, endurance exercise training remains the only practical strategy to protect the heart against IR injury (IRI). Moreover, although exercise is shown to mitigate aberrant mitophagy and ameliorates cardiovascular dysfunction, [19] few evidence is available concerning about cardiac muscle mitophagy and especially in patient cardiomyocytes in response to rehabilitative exercise training. ...
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Mitochondria as dynamic organelle constantly undergo fusion and fission reactions, leading to continuous reconstruction of the mitochondrial network for elongated or fragmentation shapes and ultimately the mitophagy. This mitochondrial network dynamics is sensitive to stress and different physiological conditions and plays an essential role in cell function and survival during pathophysiological conditions. There is a strong interaction between the mitochondrial network morphology and proteins involved in energy metabolism and dynamics. It is suggested that changes in cellular energy status during exercise training are due to mitochondrial network dynamics and mitophagy. Accordingly, growing evidence reveals that exercise training results in alterations in mitochondrial phenotype and dynamics that resist apoptotic stimuli and ischemia-reperfusion-induced mitochondrial damage. However, the signaling pathways of mitochondrial dynamics and mitophagy regulation during exercise training are still interesting areas of research. In this review, we focus on the recent findings addressing cellular signaling mechanisms of mitochondrial dynamics and cardiac mitophagy in response to exercise training and the pathological stimulus in heart disorders.
... Such increase of adipose tissue TG lipolysis and, presumably, IMTG, is mediated by increased catecholamine response to exercise (6). Exercise training has implications in the improvement of glycemic control in patients with type 2 diabetes mellitus and insulin sensitivity and resistance (9,42) and in the prevention of multiple sclerosis, lung diseases, Parkinson's disease, and cardiovascular diseases (31,82). Physical activity is associated with reduced cardiovascular morbidity and mortality (21,35,81) and is recommended for treatment of hyperlipidemia, which is known for being a risk of coronary heart disease (CHD) (17,66). ...
Article
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Blood lipoproteins are formed by various amounts of cholesterol (C), triglycerides (TG), phospholipids and apolipoproteins (Apos). Apo A1 is the major structural protein of high-density lipoprotein (HDL), accounting for approximately 70% of HDL protein, and mediates many of the anti-atherogenic functions of HDL. Conversely, Apo B is the predominant low-density lipoprotein (LDL) Apo and is a reliable indicator of circulating LDL, associated with higher coronary heart disease (CHD) risk. Furthermore, the Apo B/Apo A1 ratio is used as a surrogate marker of the risk of CHD related to lipoproteins. Elevated or abnormal levels of lipids and/or lipoproteins in the blood is a significant CHD risk factor and several studies strongly support the idea that aerobic exercise decreases CHD risk partially lowering serum TG and LDL-cholesterol (LDL-C) levels and increasing HDL-C levels. Exercise also exerts an effect on HDL-C maturation and composition and on reverse C transport from peripheral cells to the liver, in order to favor its catabolism and excretion. This process prevents atherosclerosis and several studies showed that exercise training increases heart lipid metabolism and protects against cardiovascular disease. The purpose of this review is to assess the effects of endurance training on the nontraditional lipid biomarkers including Apo B, Apo A1, Apo B/Apo A1 ratio in CHD.
... Vessel endothelium injury due to reactive oxygen species plays a key role in the pathogenesis of cardiovascular disorders [3]. Myocardial ischemia-reperfusion injury is characterized as a major factor in the morbidity and mortality correlated with coronary artery disease [4]. Acute myocardial infarction is a major cause of disability and death worldwide [5]. ...
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Background/aims: In recent years, microRNA-495 (miR-495) has been reported to be a tumor-suppressor miR that is down-modulated in cancers. However, its potential mechanism remains unknown. Therefore, this study aimed to demonstrate the role of miR-495 in cardiac microvascular endothelial cell (CMEC) injury and inflammatory reaction by mediating the pyrin domain-containing 3 (NLRP3) inflammasome signaling pathway. Methods: Overall, 40 mice were assigned into myocardial ischemia/reperfusion injury (MIR) and sham groups. After model establishment, the levels of troponin T (TnT), troponin I (TnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatine kinase isoenzyme MB (CK-MB), myoglobin (MYO), tumor necrosis factor-alpha (TNF-α), and interleukin 1beta (IL-1β) were detected by Enzyme-Linked Immunosorbent Assay (ELISA). Apoptosis was evaluated using Terminal deoxy (d)-UTP nick end labeling (TUNEL) staining, the level of NLRP3 protein was determined by immunohistochemical assay, and miR-495 was detected by in situ hybridization (ISH). The infarct size was determined using 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. The expression of miR-495 and the mRNA and protein levels of NLRP3, TNF-α, IL-1β, IL-18 and caspase-1 were evaluated by RT-qPCR and western blot analysis. After transfection, the cells were treated with a miR-495 mimic, a miR-495 inhibitor, or siNLRP3. Cell proliferation was measured by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and cell cycle and apoptosis by flow cytometry. Results: Mice with myocardial I/R injury had elevated levels of TnT, TnI, NT-proBNP, CK-MB, MYO, TNF-α and IL-1β; enhanced cell apoptosis; increased expression of NLRP3, TNF-α, IL-1β, IL-18 and caspase-1; and decreased miR-495 expression. MiR-495 was confirmed to target NLRP3. Moreover, miR-495 reduced the mRNA and protein levels of NLRP3, TNF-α, IL-1β, IL-18 and caspase-1, inhibited cell apoptosis and decreased cells at the G0/G1 phase while improving cell proliferation and increasing cells at the S phase. However, the effects of NLRP4 were proved to be reciprocal. Conclusion: In conclusion, the current study indicated that miR-495 improved CMEC injury and inflammation by suppressing the NLRP3 inflammasome signaling pathway.
... The HSP family, especially HSP72, is believed to provide myocardial protection against increased ROS generation during I/R events [39,40]. HSP72 is strongly activated during I/R insults and triggers a counter-regulatory action against cellular oxidative damage by modulating the SOD [40] and CAT [41] activities. ...
... Regular exercise has been recognized as an effective method to improve heart function and reduce cardiovascular disease and mortality. Different animal models and human epidemiological studies suggest that exercise can have significant cardioprotective effects [22][23][24]. These protective mechanisms can be listed as maximum oxygen consumption, improvements in cardiorespiratory capacity, lipid profile and endothelial functions, as well as increases in mitochondrial antioxidant capacity and the number of capillaries [25]. ...
Article
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The effects of swimming exercise on age-associated electrical changes in female rat hearts were investigated. Four- and 24-month-old Wistar female rats were divided into three groups as follows: sedentary young, sedentary old and exercise old. Swimming exercise was performed for 8 weeks (60 min/day, 5 days/week). All recordings were taken from freshly isolated left ventricular myocytes of rat heart. Aging caused a significant increase in the size of myocytes; swimming exercise did not affect this change. The repolarization period of the action potential was prolonged in aged myocytes, but exercise training had no effect on this prolongation. Exercise suppressed the transient outward potassium currents, while the inactivation and reactivation kinetics did not change between the groups. Moreover, aging caused suppression in the inward rectifier potassium currents, and exercise increased this suppression. Consequently, changes in the action potential and potassium currents may contribute to the impaired cardiac function in the elderly female myocardium, and swimming exercise is not an effective strategy in reversing these electrical changes.
... Continuation of exercise beyond that point might put the subject at risk of developing myocardial ischaemia and angina pectoris (173). Although numerous studies have reported that exercise preconditioning is associated with increasing tolerance to I/R injury (174)(175)(176)(177)(178), the maximal hypoxic exercise often disrupts the prooxidant-antioxidant balance in myocardial tissue and potentially jeopardizes cardiac functions. Additionally, heavy exercise causes ischaemia associated ventricular arrhythmias (179). ...
Article
Exercise conducted at an optimum training load is usually beneficial for the overall health of an individual. However, an unaccustomed intense exercise carried out by untrained individuals or elite athletes during over-training and/or competition-related stress often bear inevitable cardiovascular risks. Although many alterations occurring in the cardiovascular system during exercise are the results of training adaptations, sudden cardiovascular deaths reported in competitive athletes is a matter of grave concern. Several oxidative biomarkers that depict the underlying structural and functional impairment of the myocardial tissue have been identified in the individuals subjected to extensive exercise. The exercise-mediated cardiomyopathy is free radical related and also associated with pro-inflammatory response. In this review we will highlight the possible role of melatonin in obviating irrevocable oxidative cardiovascular injury triggered by extensive exercise stress. Melatonin effectively reduces exercise-induced lipid peroxidation, restores natural cellular antioxidant pool and supresses the innate immune cascade reaction that, otherwise, jeopardize cardiovascular integrity. Melatonin blocks the IKK/IκB/NFκB signaling as well as suppress iNOS and COX-2 mediated inflammation in cardiac tissue. In addition, melatonin reduces blood lactate accumulation and accelerates glucose utilization, thereby, promoting energy metabolism in athletes during their training and competition. Physical exertion associated overheating and the resultant sympathetic outflow impede cardiovascular homeostasis. Melatonin not only attenuates the sympathomedullary stimulation but also protects the cardiac cells from the cytotoxic effect of catecholamines. The available information regarding the efficacy of melatonin in amelioration of exercise-driven oxidative insult in cardiac tissue has been discussed and summarized.
... These changes may reduce mitochondrial biogenesis, downregulate gene levels, alter Ca 2+ and proton flux, and inevitably lead to organelle degeneration (29). Elevated intracellular Ca 2+ levels, together with other factors, lead to increased oxidative stress and the opening of mitochondrial permeability transition pores (MPTP), a process that releases proapoptotic compounds and subsequently activates caspases, resulting in mitochondrial swelling, tissue damage, and myocardial apoptosis (30). As mitochondria are finely regulated by a variety of regulatory molecules and exert a strong influence on life activities, there is an urgent need to elucidate their quality control mechanisms in detail to protect the myocardium from dysfunctional mitochondria. ...
Article
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Regular moderate-intensity exercise elicits benefit cardiovascular health outcomes. However, exhaustive exercise (EE) triggers arrhythmia, heart failure, and sudden cardiac death. Therefore, a better understanding of unfavorable heart sequelae of EE is important. Various mechanisms have been postulated for EE-induced cardiac injury, among which mitochondrial dysfunction is considered the cardinal machinery for pathogenesis of various diseases. Mitochondrial quality control (MQC) is critical for clearance of long-lived or damaged mitochondria, regulation of energy metabolism and cell apoptosis, maintenance of cardiac homeostasis and alleviation of EE-induced injury. In this review, we will focus on MQC mechanisms and propose mitochondrial pathophysiological targets for the management of EE-induced myocardial injury. A thorough understanding of how MQC system functions in the maintenance of mitochondrial homeostasis will provide a feasible rationale for developing potential therapeutic interventions for EE-induced injury.
... Besides the alteration of general cardiovascular risk factors (e.g., high blood pressure or hypercholesterolemia), exercise confers direct protection against I/R injury of a distant organ. This protective effect may include the development of collateral arteries, alterations in circulation, expression of endoplasmic reticulum stress proteins, and the modulation of cyclooxygenase-2 activity, heat shock proteins, and ATP-sensitive potassium channels [14,15]. Exercise also induces antioxidant effects [16][17][18] and diminishes the increased susceptibility of cardiac mitochondria to undergo permeability transition pore opening [19]. ...
Article
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There is a growing body of evidence showing the importance of physical activity against acute ischemic events in various organs. Ischemia/reperfusion injury (I/R) is characterized by tissue damage as a result of restriction and subsequent restoration of blood supply to an organ. Oxidative stress due to increased reactive oxygen species formation and/or insufficient antioxidant defense is considered to play an important role in I/R. Physical activity not only decreases the general risk factors for ischemia but also confers direct anti-ischemic protection via myokine production. Myokines are skeletal muscle-derived cytokines, representing multifunctional communication channels between the contracting skeletal muscle and other organs through an endocrine manner. In this review, we discuss the most prominent members of the myokines (i.e., brain-derived neurotrophic factor (BDNF), cathepsin B, decorin, fibroblast growth factors-2 and-21, follistatin, follistatin-like, insulin-like growth factor-1; interleukin-6, interleukin-7, interleukin-15, irisin, leukemia inhibitory factor, meteorin-like, myonectin, musclin, myostatin, and osteoglycin) with a particular interest in their potential influence on reactive oxygen and nitrogen species formation or antioxidant capacity. A better understanding of the mechanism of action of myokines and particularly their participation in the regulation of oxidative stress may widen their possible therapeutic use and, thereby, may support the fight against I/R.
... Physical exercise has many positive effects on cardiovascular health. Exercise training protects the myocardium against ischemia-reperfusion injury, reduces myocardial oxidative damage and improves cardiac function after IRI onset [343][344][345]. Various factors derived from the heart and other tissues are responsible for this effect, but much remains to be clarified. ...
Article
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The majority of cardiovascular deaths are associated with acute coronary syndrome, especially ST-elevation myocardial infarction. Therapeutic reperfusion alone can contribute up to 40 percent of total infarct size following coronary artery occlusion, which is called ischemia-reperfusion injury (IRI). Its size depends on many factors, including the main risk factors of cardiovascular mortality, such as age, sex, systolic blood pressure, smoking, and total cholesterol level as well as obesity, diabetes, and physical effort. Extracellular vesicles (EVs) are membrane-coated particles released by every type of cell, which can carry content that affects the functioning of other tissues. Their role is essential in the communication between healthy and dysfunctional cells. In this article, data on the variability of the content of EVs in patients with the most prevalent cardiovascular risk factors is presented, and their influence on IRI is discussed.
... Altogether, we find that endurance training induces a heat shock response and HSP accumulation across tissues, which can explain some of the cytoprotective effects associated with exercise 33,34 . The alteration of HSPs primarily at the protein level illustrates the importance of measuring multiple omes to fully understand the endurance training response. ...
Preprint
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Regular exercise promotes whole-body health and prevents disease, yet the underlying molecular mechanisms throughout a whole organism are incompletely understood. Here, the Molecular Transducers of Physical Activity Consortium (MoTrPAC) profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome, and immunome in whole blood, plasma, and 18 solid tissues in Rattus norvegicus over 8 weeks of endurance exercise training. The resulting data compendium encompasses 9466 assays across 19 tissues, 25 molecular platforms, and 4 training time points in young adult male and female rats. We identified thousands of shared and tissue- and sex-specific molecular alterations. Temporal multi-omic and multi-tissue analyses demonstrated distinct patterns of tissue remodeling, with widespread regulation of immune, metabolism, heat shock stress response, and mitochondrial pathways. These patterns provide biological insights into the adaptive responses to endurance training over time. For example, exercise training induced heart remodeling via altered activity of the Mef2 family of transcription factors and tyrosine kinases. Translational analyses revealed changes that are consistent with human endurance training data and negatively correlated with disease, including increased phospholipids and decreased triacylglycerols in the liver. Sex differences in training adaptation were widespread, including those in the brain, adrenal gland, lung, and adipose tissue. Integrative analyses generated novel hypotheses of disease relevance, including candidate mechanisms that link training adaptation to non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health, and tissue injury and recovery. The data and analysis results presented in this study will serve as valuable resources for the broader community and are provided in an easily accessible public repository ( https://motrpac-data.org/ ). Highlights Multi-tissue resource identifies 35,439 analytes regulated by endurance exercise training at 5% FDR across 211 combinations of tissues and molecular platforms. Interpretation of systemic and tissue-specific molecular adaptations produced hypotheses to help describe the health benefits induced by exercise. Robust sex-specific responses to endurance exercise training are observed across multiple organs at the molecular level. Deep multi-omic profiling of six tissues defines regulatory signals for tissue adaptation to endurance exercise training. All data are available in a public repository, and processed data, analysis results, and code to reproduce major analyses are additionally available in convenient R packages.
... Increasing evidence, including clinical trials and animal experiments, shows that moderate exercise can mediate cardiac protective role against injuries such as endothelial dysfunction [9], myocardial ischemia-reperfusion injury (IRI) [10,11], hypertension [12], heart failure [13,14], and pathological cardiac remodeling [15,16]. However, exercise training can induce the ROS production and subsequent oxidative stress, which may contribute to a series of changes that occur during exercise [17]. ...
Article
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Exercise is a preferred strategy for improving cardiac function, especially for patients with cardiovascular diseases. Increasing evidence indicates that oxidative stress is involved in exercise-induced cardioprotection, while the underlying mechanism remains unclear. Furthermore, the effect of antioxidant supplementation during or post-exercise still exists despite divergences. To explore the effect of oxidative stress and antioxidant supplementation on cardiovascular homeostasis during or post-exercise, we take insights into the progress of exercise-induced oxidative stress, antioxidant supplementation, and cardiovascular homeostasis. In particular, antioxidants such as vitamin C or E, gamma-oryzanol, and other natural antioxidants are discussed concerning regulating exercise-associated oxidative stress. Additionally, our present study reviewed and discussed a meta-analysis of antioxidant supplementation during exercise. Overall, we take an insight into the essential biological adaptations in response to exercise and the effects of antioxidant supplementation on cardiac function, which aid us in giving recommendations on antioxidant supplementation for exercisers and exercised people. A better understanding of these issues will broaden our knowledge of exercise physiology. Graphical abstract
... High-intensity exercise without the use of music causes damage, but such damage has the potential to improve cardiac performance (Cassidy et al., 2016). Remodeling occurs after 1-5 minutes of ischemia, resulting in fibrillation without cell death in ventricular contraction performance, and ischemic and remodeling rates are at the highest when ischemic occured over 20 minutes exercise (Powers et al., 2008). High-intensity exercise will improve Cyclic Adenosine Monophosphate (cAMP). ...
Conference Paper
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Music with exercise could improve left ventricular performance, thereby decreasing the extent of tissue damage in the left ventricle of the heart. The study aimed to measure sports intervention with fast tempo music (Allegro) on the extent of cellular damage to the left ventricular myocardial tissue of the heart. This study used an experimental research design using a Random Controlled Group Posttest-Only Design. A control group was played Allegro music, a moderate sports group was played Allegro music, and a high-intensity sports group was played Allegro music using Wistar white rats of the male sex. Sport was performed using a special treadmill for mice for ten weeks. Data analysis was performed using ANOVA test. The results of this study show that there was a difference in left ventricular wall thickness in the heart between the control group and allegro music group, moderate exercise group with allegro music, and high-intensity group with allegro music (F=19,636; p=0.001). This study showed that high-intensity exercise with allegro music has the potential to improve the health of the left ventricle of the heart.
... Hearts were removed immediately and held at − 20 °C for 20 min. The heart was cut transversely to a millimeter of thickness using a rat heart matrix and the heart slices immersed in 2,3,5 triphenyltetrazolium chloride (TTC, Sigma-Aldrich, St Louis, MO, USA) for 20 min at 37 °C and then fixed in 10% formaldehyde [18,19]. After 24 h, the heart slices were scanned. ...
Article
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The formation of new blood vessels in the ischemic area is a fundamental strategy that can reduce myocardial infarction-induced damage by mitigating hypoxia. This paper set out to investigate the cardioprotective effect of high-intensity interval training preconditioning and L-arginine supplementation on myocardial ischemia–reperfusion-induced angiogenesis and oxidative stress. 50 male rats were randomly distributed into following groups: (1) Sham, (2) Sedentary control (Con, n = 10), 3) L-arginine treatment (La, n = 10), (4) High-Intensity Interval Training (HIIT, n = 10), and High-Intensity Interval Training plus L-arginine supplementation (HIIT + La, n = 10). Rats in the training groups performed high-intensity interval training for 8 weeks (5 day per week). Subjects in La and HIIT + La groups received L-arginine in drinking water (4 g/L). 72 h after treatments, all subjects underwent myocardial ischemia–reperfusion operation. Cardiac function, angiogenesis, stress oxidative, and infarction size were measured after reperfusion. Results showed exercise training and L-arginine supplementation promoted Cat and GSH activities and decreased MDA activity following myocardial ischemia–reperfusion injury in non-infarcted area. Compared with the con group, VEGF and Ang-1 as well as Ang-1 to Ang-2 ratio following myocardial ischemia–reperfusion in the non-infarct area were higher in La + HIIT group. Meanwhile, capillary density and capillary-to-muscle fiber ratio were higher in response to training and L-arginine supplementation. HIIT and L-arginine alone and synergistically decreased ischemia–reperfusion-induced infarction size. Cardiac output and stroke volume ameliorate in response to exercise training and L-arginine supplementation. Taken together, exercise preconditioning and l-arginine supplementation improved left ventricular function following ischemia–reperfusion by stress oxidative mitigation and angiogenesis amelioration.
... This hypertrophic phenotype was related with increased citrate synthase activity, which together with the increased levels of PGC-1α and mtTFA is suggestive of augmented mitochondrial biogenesis (Fig. 3). Such benefic effect of exercise was already reported in the set of diabetic cardiomyopathy and atherosclerosis [22,23]. Mitochondrial biogenesis induced by exercise training seems to be related to metabolic remodeling towards increased glucose oxidation instead of fatty acids. ...
Article
Limiting cancer-induced cardiac damage has become an increasingly important issue to improve survival rates and quality of life. Exercise training has been shown to reduce cardiovascular complications in several diseases; however, its therapeutic role against cardiovascular consequences of cancer is in its infancy. In order to add new insights on the potential therapeutic effect of exercise training on cancer-related cardiac dysfunction, we used an animal model of urothelial carcinoma submitted to 13 weeks of treadmill exercise after 20 weeks of exposure to the carcinogenic N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). Data showed that 13 weeks of treadmill exercise reverted cancer-induced cardiomyocytes atrophy and fibrosis, improved cardiac oxidative capacity given by citrate synthase activity and MnSOD content, and increased the levels of the mitochondrial biogenesis markers PGC-1α and mtTFA. Moreover, exercise training reverted cancer-induced decrease of cardiac c-kit levels suggesting enhanced regenerative ability of heart. These cardiac adaptations to exercise were related to a lower incidence of malignant urothelial lesions and less signs of inflammation. Taken together, data from the present study support the beneficial effect of exercise training when started after cancer diagnosis, envisioning the improvement of the cardiovascular function.
... Exercise training is a kind of mechanical and stress stimulation. Human epidemiological studies have shown that regular exercise can reduce the risk of death during myocardial ischemia-reperfusion injury [72]. Meanwhile, the studies in animal models have also shown that regular endurance exercise (running or swimming training) may mimic the favorable cardioprotective effect of ischemia preconditioning and attenuate cardiomyocyte death under the circumstance of myocardial ischemia-reperfusion injury [73][74][75][76]. ...
Chapter
Cardiovascular diseases (CVDs) are a group of common disorders associated with heart and its blood vessels, with the characteristics of high incidence or high mortality and poor prognosis, especially for elderly population. CVD is the leading cause of global mortality and the dominant contributor for reduced quality of life among people with chronic diseases all over the world. CVDs are usually composed of hypertension, atherosclerosis, cardiomyopathy, myocardial ischemia–reperfusion injury, and other complications. According to the statistics from the WHO report in 2017, approximately 17.8 million people are died of CVDs each year, accounting for 31% of all deaths worldwide, and CVDs could result in 35.6 million people lived with disability [1]. Obesity, drug abuse, hyperlipidemia, high blood pressure, reduced physical activity, smoking, and alcohol drinking are important factors for inducing CVDs. The current incidence of CVDs shows a rapidly increasing trend, which could result in the significant impact on the quality of life of these patients and the larger burden on social and medical system.
... Regular physical activity is important not only for mental health but also for physical health. Exercise training has implications in epigenetic regulation [1], aging [2], improvement of glycemic control in patients with type 2 diabetes mellitus and insulin sensitivity and resistance [3,4], prevention of cardiovascular diseases [5][6][7], and others such as multiple sclerosis, lung diseases, Parkinson's disease, and so on [8][9][10][11][12][13]. Thus, the study of lipid metabolism is a key element to understand how physical activity influences our health and, in particular, that of professional athletes. ...
Article
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Since the lipid profile is altered by physical activity, the study of lipid metabolism is a remarkable element in understanding if and how physical activity affects the health of both professional athletes and sedentary subjects. Although not fully defined, it has become clear that resistance exercise uses fat as an energy source. The fatty acid oxidation rate is the result of the following processes: (a) triglycerides lipolysis, most abundant in fat adipocytes and intramuscular triacylglycerol (IMTG) stores, (b) fatty acid transport from blood plasma to muscle sarcoplasm, (c) availability and hydrolysis rate of intramuscular triglycerides, and (d) transport of fatty acids through the mitochondrial membrane. In this review, we report some studies concerning the relationship between exercise and the aforementioned processes also in light of hormonal controls and molecular regulations within fat and skeletal muscle cells.
... Exercise training is considered beneficial to the cardiovascular system. Regular physical exercise has been shown to improve physical health, improve cardiac function and strengthen the cellular mechanisms that prevent cardiac damage [21][22][23]. Regular exercise throughout the life reduces cardiovascular diseases and improves functional ability [24]. Studies have shown that voluntary exercise throughout the life can improve age-related gene expression changes in the heart, suggesting that exercise can maintained the heart young [25]. ...
Article
Aging is the most important risk factor for cardiovascular diseases. Although exercise is known to be beneficial for the health of aging heart, the optimal exercise training intensity to prevent natural aging-induced cardiac damage has not been defined. In this study, we used 32-week-old male mice and randomly divided them into three groups, namely, untrained (UNT) mice, moderate-intensity exercise training (MET) mice, and high-intensity interval training (HIIT) mice. Mice in the two exercise training groups were subjected to exercise 5 days per week for 24 consecutive weeks. Metabolic characteristics, cardiac function and morphology, myocardial remodeling, myocardial fibrosis (collagen III, α-SMA, and TGF-β), oxidative stress (NRF2, HO-1, SOD, and NOX4), and apoptosis (BAX, Bak, Bcl-2, and Bcl-XL) were analyzed 24 weeks after the different treatments. MET improved cardiac function and reduced myocardial remodeling, myocardial fibrosis, and oxidative stress in the aging heart. MET treatment exerted an anti-apoptotic effect in the heart of the aging mice. Importantly, HIIT did not protect against cardiac damage during the natural aging process. These findings suggest that MET may be one of the main methods to prevent cardiac damage induced by natural aging.
... Exercise training at the appropriate intensity can induce autophagy to degrade metabolic wastes so as to maintain the steady state of the cell [19]. Aerobic exercise also can induce autophagy to protect myocardial cells [99,100]. According to the previous study, LC3-II/LC3-I ratio in mouse myocardium is more significantly higher in the exercise group when compared with the nonexercise group, suggesting that exercise training can reduce myocardial infarction during myocardial cell injury in mice, enhance cardiovascular function by improving autophagy, and promote the degradation of damaged proteins [23]. ...
Article
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High altitude training is one of the effective strategies for improving aerobic exercise performance at sea level via altitude acclimatization, thereby improving oxygen transport and/or utilization. But its underlying molecular mechanisms on physiological functions and exercise performance of athletes are still vague. More recent evidence suggests that the recycling of cellular components by autophagy is an important process of the body involved in the adaptive responses to exercise. Whether high altitude training can activate autophagy or whether high altitude training can improve exercise performance through exercise-induced autophagy is still unclear. In this narrative review article, we will summarize current research advances in the improvement of exercise performance through high altitude training and its reasonable molecular mechanisms associated with autophagy, which will provide a new field to explore the molecular mechanisms of adaptive response to high altitude training.
... Beneficial impacts of exercise on cardiovascular structure and function are also seen in CVD, such as ischemia-reperfusion injury (IRI) and chronic heart failure (CHF). Endurance exercise has been reported to reduce oxidative stress and structural damage in IRI, thereby preventing myocardial dysfunction in animal studies [87][88][89][90][91][92]. However, the role of biological sex (if any) on the effects of exercise on myocardial oxidative stress is not clear. ...
Article
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Cardiovascular diseases (CVD) remain the leading cause of death in men and women. Biological sex plays a major role in cardiovascular physiology and pathological cardiovascular remodeling. Traditionally, pathological remodeling of cardiovascular system refers to the molecular, cellular, and morphological changes that result from insults, such as myocardial infarction or hypertension. Regular exercise training is known to induce physiological cardiovascular remodeling and beneficial functional adaptation of the cardiovascular apparatus. However, impact of exercise-induced cardiovascular remodeling and functional adaptation varies between males and females. This review aims to compare and contrast sex-specific manifestations of exercise-induced cardiovascular remodeling and functional adaptation. Specifically, we review (1) sex disparities in cardiovascular function, (2) influence of biological sex on exercise-induced cardiovascular remodeling and functional adaptation, and (3) sex-specific impacts of various types, intensities, and durations of exercise training on cardiovascular apparatus. The review highlights both animal and human studies in order to give an all-encompassing view of the exercise-induced sex differences in cardiovascular system and addresses the gaps in knowledge in the field.
... Given the myriad of adverse health impacts, the 2011 American Heart Association Effectiveness-based Guidelines for the Prevention of Cardiovascular Disease in Women lists physical inactivity as a risk factor, as strong as smoking, for the development of cardiovascular disease and associated sequela including obesity [44]. Among the strategies proposed to prevent CVD, exercise is the most effective [45]. The cardiovascular benefits from exercise are derived from: a) an increase in endothelium-dependent vasodilation following an increase in vascular concentrations of nitric oxide (NO) [46] and endothelium-dependent hyperpolarization [47]; b) a decrease in vasoconstrictor responses either by a reduction in plasma endothelin-1 concentrations [48], or a decrease in the expression of the angiotensin II receptor [49]; c) a modulation in the production/clearance of reactive oxygen species [49,50]; d) a reduction in sympathetic outflow at rest or during conditions that increase sympatho-excitation [51]; and e) an enhancement of the arterial baroreflex sensitivity [52]. ...
Article
The Developmental Origins of Health and Disease suggest the in utero environment programs offspring obesity and cardiovascular disease. Therefore, there is a need to implement safe therapeutic interventions that do not involve the intake of medications or biological products during pregnancy that can improve maternal and fetal health. Prenatal exercise is established to promote maternal and fetal health. It is generally recommended that women accumulate at least 150 minutes per week of moderate-intensity exercise. It has been demonstrated that prenatal exercise maintains healthy weight gain and improves maternal glucose control, maternal cardiac autonomic control, placental efficiency (increases angiogenesis, downregulates genes involved in fatty acid transport and insulin transport across the placenta, and upregulates genes involved in amino acid transport across the placenta), and oxidative stress. These adaptations following exercise improve maternal metabolism and provide adequate uteroplacental perfusion. In this review, we will focus on exercise as a therapeutic intervention to optimize fetal weight. It has been established that prenatal exercise does not increase the risk of having a small for gestational age baby. To the contrary, prenatal exercise has been associated with the prevention of excessive fat accumulation in the newborn and the maintenance of fetal muscle mass.
... En effet, il est aujourd'hui largement décrit que l'exercice régulier réduit le risque de décès lors de l'IR myocardique en augmentant les défenses enzymatiques antioxydantes (MnSOD, Cu-ZnSOD et GPx) (Hamilton et al., 2001;Powers et al., 1998). Ceci serait notamment expliqué par l'activation du facteur nucléaire de transcription Nrf2 en réponse au stress oxydant aigu produit par chaque exercice physique (Done and Traustadóttir, 2016;Lee et al., 2012b;Powers et al., 2008). Dans notre travail, en accord avec des études précédentes , nous observons une diminution de la production d'ERO au cours de la reperfusion post-ischémique dans les coeurs d'animaux entrainés. ...
Thesis
L’infarctus du myocarde constitue la première cause de mortalité cardiovasculaire. A ce jour, la seule stratégie permettant de limiter la mort cellulaire au cours de l’ischémie cardiaque est la reperfusion. Néanmoins, elle est à l’origine de lésions qui lui sont propres. L’établissement d’un cercle vicieux entre la surproduction d’espèces réactives oxygénées mitochondriales (EROmt) et la surcharge calcique (Ca2+) matricielle semble être un acteur clé de l’exacerbation de la mort cellulaire dans les premiers instants de la reperfusion. Dans ce contexte, l’objectif de ce travail de thèse a été de développer et/ou de mieux comprendre les mécanismes sous-jacents de stratégies naturelles permettant de limiter l’établissement de ce cercle vicieux pour permettre une protection des mitochondries au cours de l’ischémie-reperfusion. Notre première stratégie a été d’identifier dans la nature des molécules antioxydantes dont les propriétés physico-chimiques permettent de cibler le stress oxydant mitochondrial. Nous avons pu identifier un antioxydant naturel, la sinapine dont les propriétés chimiques pourraient lui conférer un tropisme mitochondrial. On a ainsi pu démontrer in vitro, in cellulo, ex vivo et in vivo que la sinapine était capable de cibler le stress oxydant mitochondrial et ainsi diminuer la sensibilité du cœur à l’IR. La deuxième étude de ce travail de thèse consistait à mieux identifier les mécanismes cellulaires sous-jacents à la cardioprotection par l’exercice physique. Une attention toute particulière a été portée sur le rôle clé joué par la signalisation du monoxyde d’azote (NO) au niveau mitochondrial. En effet, le NO est bien décrit comme pouvant moduler la production d’EROmt et comme permettant de protéger le cœur au cours de l’IR. Néanmoins, à ce jour, l’impact de l’exercice sur la signalisation eNOS-NO au niveau mitochondrial est mal connu. Nous avons pu observer qu’un entraînement modéré de 5 semaines était à l’origine d’une translocation de la eNOS au niveau des mitochondries et que celle-ci était associée à une augmentation de la biodisponibilité du NO au niveau mitochondrial et à une modification du s-nitrosoprotéome. Enfin, nous avons pu montrer que la S-nitrosylation joue un rôle clé dans la protection des mitochondries en situation de stress permettant de mimer l’ischémie-reperfusion. Mots
... Exercise has been shown to protect the heart against a wide range of insults including sepsis, 23 ischemia-reperfusion injury, 24 as well as cancer-induced cardiac cachexia. 25 Studies have consistently shown that both endurance and resistance exercise training attenuate cardiac dysfunction in animals treated with DOX. ...
Article
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Introduction: Doxorubicin (DOX) is a widely used chemotherapeutic agent with known cardiotoxic properties, while calorie restriction (CR) and exercise have well-documented cardioprotective effects. No studies have investigated the effects of CR alone or the combined effects of CR and exercise on DOX cardiotoxicity. Methods: Rats were divided into 4 groups based on their food intake (ad libitum or CR) and activity (sedentary or voluntary wheel running [WR]). After completing a 16-week treatment, animals received either DOX (15 mg/kg) or saline (SAL) and cardiac function was measured 5 days after treatment. Chromatography was used to quantify left ventricular DOX accumulation. Results: Left ventricular developed pressure (LVDP), end systolic pressure (ESP), and left ventricular maximal rate of pressure development (dP/dtmax) were significantly higher in the CR + DOX group when compared with DOX. Fractional shortening, LVDP, ESP, dP/dtmax, and dP/dtmin were significantly higher in the CR + WR + DOX group compared with the DOX group. In addition, the CR + WR + DOX group showed significantly higher LVDP and ESP compared with the WR + DOX group. DOX accumulation in the heart was 5-fold lower ( P < .05) in the CR + WR + DOX group compared with the DOX group. Conclusion: This is the first study to demonstrate that CR can reduce cardiac DOX accumulation, and confirms the protective role of CR against DOX-induced cardiac dysfunction. Our data also show that combining a known cardioprotective intervention, exercise training, with CR results in additive benefits in the protection against DOX cardiotoxicity.
Article
Discovering an effective approach to limit infarction size after ischemia-reperfusion has a clinical importance in diabetics. We investigated the anti-myocardial ischemia-reperfusion injury effect of resistance training and Crataegus oxyacantha extract on diabetic rats. To this end, 50 male Wistar rats were randomly divided into 5 groups: the sedentary control (SC), sedentary diabetic (SD), resistance trained diabetic (RD), diabetic plus C. oxyacantha extract treatment (CD) and resistance trained diabetic plus C. oxyacantha extract treatment (RCD) groups. Animals in trained groups were subjected to progressive resistance training program with the use of a ladder (5 days/week, for 10 weeks). C. oxyacantha extract rats were treated with 100 mg/kg body weight of the extract using a gavage every day for 10 weeks. After treatments, rats were subjected to ischemia via LAD artery ligation for 30 min followed by 90 min reperfusion. The heart was collected following the ischemia-reperfusion and analyzed for oxidative stress and ischemia-reperfusion injury. Compared to the SC group, LDH, CK-MB and infarction size in the SD group were significantly higher, whereas injury indices in the RCD group were significantly lower than those in the SD group. GPx and MPO levels after reperfusion increased and decreased, respectively in response to training and C. oxyacantha. These findings suggest that 10 weeks resistance training and C. oxyacantha can synergistically decrease ischemia-reperfusion injury, and this mechanism may be related to a reduction in oxidative stress which is normally associated with ischemia-reperfusion.
Article
Aim We investigated the effects of high-intensity interval and continuous short-term exercise on body composition and cardiac function after myocardial ischemia-reperfusion injury (IRI) in obese rats. Methods Rats fed with a standard chow diet (SC) or high-fat diet (HFD) for 20 weeks underwent systolic blood pressure (SBP), glycemia and dual-energy X-ray absorptiometry analyses. Then, animals fed with HFD were subdivided into three groups: sedentary (HFD-SED); moderate-intensity continuous training (HFD-MICT); and high-intensity interval training (HFD-HIIT). Exercised groups underwent four isocaloric aerobic exercise sessions, in which HFD-MICT maintained the intensity continuously and HFD-HIIT alternated it. After exercise sessions, all groups underwent global IRI and myocardial infarct size (IS) was determined histologically. Fat and muscle mass were weighted, and protein levels involved in muscle metabolism were assessed in skeletal muscle. Results HFD-fed versus SC-fed rats reduced lean body mass by 31% (P < 0.001), while SBP, glycemia and body fat percentage were increased by 10% (P = 0.04), 30% (P = 0.006) and 54% (P < 0.001); respectively. HFD-induced muscle atrophy was restored in exercised groups, as only HFD-SED presented lower gastrocnemius (32%; P = 0.001) and quadriceps mass (62%; P < 0.001) than SC. PGC1-α expression was 2.7-fold higher in HFD-HIIT versus HFD-SED (P = 0.04), whereas HFD-HIIT and HFD-MICT exhibited 1.7-fold increase in p-mTORSer2481 levels compared to HFD-SED (P = 0.04). Although no difference was detected among groups for IS (P = 0.30), only HFD-HIIT preserved left-ventricle developed pressure after IRI (+0.7 mmHg; P = 0.9). Significance Short-term exercise, continuous or HIIT, restored HFD-induced muscle atrophy and increased mTOR expression, but only HIIT maintained myocardial contractility following IRI in obese animals.
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Although physical exercise is known to reduce size of infarction, incidence of ventricular arrhythmias, and to improve heart function, molecular mechanisms of this protection are not fully elucidated. We explored the hypothesis that voluntary running, similar to adaptive interventions, such as ischemic or remote preconditioning, may activate components of pro-survival (RISK) pathway and potentially modify cell proliferation. Sprague-Dawley adult male rats freely exercised for 23 days in cages equipped with running wheels, while sedentary controls were housed in standard cages. After 23 days, left ventricular (LV) myocardial tissue samples were collected for the detection of expression and activation of RISK proteins (WB). The day before, a marker of cell proliferation 5-bromo-2'-deoxyuridine (BrdU) was given to all animals to detect its incorporation into DNA of the LV cells (ELISA). Running increased phosphorylation (activation) of Akt, as well as the levels of PKCε and phospho-ERK1/2, whereas BrdU incorporation into DNA was unchanged. In contrast, exercise promoted pro-apoptotic signaling - enhanced Bax/Bcl-2 ratio and activation of GSK-3β kinase. Results suggest that in the rat myocardium adapted to physical load, natural cardioprotective processes associated with physiological hypertrophy are stimulated, while cell proliferation is not modified. Up-regulation of pro-apoptotic markers indicates potential induction of cell death mechanisms that might lead to maladaptation in the long-term.
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Proteomics and metabolomics research offers a quantitative measurement of metabolic profiles associated with exercise and identifies metabolic signatures of athletes from different sporting disciplines. Molecular biomarkers include peptides, proteins, amino acids, carbohydrates, lipids, and xenobiotics. Collectively, these metabolites capture the molecular pathways underlying whole body physiology including nutrition, energy generation, oxidative stress scavenging mechanisms, and hormonal balance. This chapter aims to review the recent literature investigating potential proteomic and metabolomic biomarkers associated with exercise, endurance, and power sports and discuss their functional relevance in relation to athletes’ performance, training, recovery from injury and overall health.
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New findings: What is the central question of this study? Can a short-term of HIIT contribute to the reduction of IR injury by enhancing the levels of Klotho and its related axes, including myocardial TRPC6 expression, and antioxidant defense as novel possible mechanisms to EICP against IR injury? What is the main finding and its importance? The increasing of plasma and myocardial levels of Klotho as a result of preconditioning with HIIT and preventing a significant reduction of Klotho during IR injury can promote cardioprotection and reduce damage by attenuate the myocardial TRPC6 expression and increased antioxidant defense. Present findings may provide a new mechanism in EICP and IR injury, and Provides the knowledge to develop preventive and therapeutic approaches. Abstract: Cardiovascular disease, especially coronary artery disease remains a major cause of morbidity and mortality in the world and ischemia-reperfusion (IR) insult is the main pathologic cause leads to death during these diseases. Exercise training is associated with a reduced risk of cardiovascular disease and cardioprotection development against IR injury. Therefore, the purpose of this study was to investigate the effect of preconditioning with high-intensity interval training on myocardial and plasma levels of klotho and its related axes as novel mechanisms to exercise-induced cardioprotection against IR injury. Seventy male Wistar rats were randomly divided into 5 groups of Control, HIIT, Sham, IR, and H-IR. The training group performed 5 sessions of high intensity interval training on the treadmill. The cardiac IR injury was induced by LAD ligation for 30 min followed by 24 h reperfusion. Infarct size and histopathological assessment of cardiac tissues were determined through Evans Blue-TTC and H&E staining respectively. We investigated lipid peroxidation and markers of cardiac injury, antioxidant enzymes, and the plasma levels of klotho using the ELISA assay. Also, myocardial levels of Klotho and TRPC6 expression was determined by western blot assay. The results demonstrated a significant increase in myocardial and plasma levels of Klotho following HIIT and a significant decrease during IR injury. The myocardial TRPC6 channels expression increased following IR. The HIIT also prevented a significant reduction of the Klotho during IR and consequently reduced the expression of TRPC6 channel in the H-IR group compared the IR group. Furthermore, HIIT decreased the infarct size, cardiac injury, lipid peroxidation, LDH, CK-MB, and cTnI and improved TAC, CAT, SOD, GPx activities and antioxidant system following IR injury. The findings of the present study suggest that HIIT improves cardioprotection against IR injury and reduces cardiac damages through an increase in myocardial and plasma levels of klotho and its related axes (TRPC6 and antioxidant defense). These findings can help to develop preventive and therapeutic approaches. This article is protected by copyright. All rights reserved.
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Background The FOXO3a/Beclin-1 pathway is an important pathway in autophagy that can be impaired in diabetic patients who are prone to cardiomyopathy. Objective The aim of this study was to investigate the effect of an 8-week endurance training program on the content of FOXO3a and Beclin-1 proteins in the heart muscle tissue of rats with type 2 diabetes. Methods This experimental study was conducted on 12 male two-month-old Sprague Dawley rats with a mean weight of 270±20 g. After diabetic induction by streptozotocin and nicotinamide, rats were randomly assigned into two groups of diabetic-exercise (n=6) and diabetic-control (n=6). The diabetic-exercise group received intervention 4 days per week, each session for 42 minutes at a speed of 10-30 m/m for 8 weeks, while the control group received no any training program. The rats did not receive any insulin treatment during the study. Collected data were analyzed using independent t-test at a significance level of P≤0.05. Findings No significant changes were observed in the content of FOXO3a (P=0.12) and Beclin-1 (P=0.34) proteins in the training group compared to the control group after intervention. Conclusion The endurance training can not affect the content of FOXO3a and Beclin-1 proteins. Therefore, it seems that endurance training may not affect autophagy signaling in the heart muscle of type 2 diabetic patients.
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Objective Cardiac mitochondrial dysfunction was found in ischemic heart disease (IHD). Hence, this study determined the effects of exercise training (ET) on cardiac mitochondrial respiration and cardiac mitochondrial quality control in IHD. Methods A narrative synthesis was conducted after searching animal studies written in English in three databases (PubMed, Web of Science, and EMBASE) until December 2020. Studies that used aerobic exercise as an intervention for at least 3 weeks and had at least normal, negative (sedentary IHD), and positive (exercise-trained IHD) groups were included. The CAMARADES checklist was used to check the quality of the included studies. Results The 10 included studies (CAMARADES score: 6–7/10) used swimming or treadmill exercise for 3–8 weeks. Seven studies showed that ET ameliorated cardiac mitochondrial respiratory function as manifested by decreased reactive oxygen species (ROS) production and increased complexes I-V activity, superoxide dismutase 2 (SOD2), respiratory control ratio (RCR), NADH dehydrogenase subunits 1 and 6 (ND1/6), Cytochrome B (CytB), and adenosine triphosphate (ATP) production. Ten studies showed that ET improved cardiac mitochondrial quality control in IHD as manifested by enhanced and/or controlled mitochondrial biogenesis, dynamics, and mitophagy. Four other studies showed that ET resulted in better cardiac mitochondrial physiological characteristics. Conclusion Exercise training could improve cardiac mitochondrial functions, including respiration, biogenesis, dynamics, and mitophagy in IHD. Systematic review registration https://www.crd.york.ac.uk/prospero/ display_record.php?RecordID=226817 , identifier: CRD42021226817.
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PURPOSE: Exercise improve myocardial cell protection and vascular function through cell repair and suppression of oxidative stress in cardiovascular diseases caused by aging. This study aimed to investigate the effect of combine exercise on HSP70 and SOD1 protein expression of aorta, skeletal muscle and myocardium in high fat diet induced obese aging rats.METHODS: Male 50-week-old Sprague Dawley rats (n=40) were divided into normal diet (ND, n=10), normal diet+exercise (NDEx, n=10), high fat diet (HFD, n=10), and high fat diet+exercise (HFDEx, n=10) groups. After six weeks on a high fat diet to induce obesity, a 12-week combine exercise program was implemented, which combine exercise (treadmill running+ladder climbing) three times a week for 45 minutes per session.RESULTS: Body weight was significantly decreased after 12 weeks combine exercise program compared to the ND group (p<.05) and HFDEx group compared to the HFD group (p<.05), respectively. After completing the 12-week exercise program, heat shock protein 70 (HSP70) and superoxide dismutase 1 (SOD1) expressions were significantly (p<.05) higher in the NDEx group compared to the ND group in the myocardium. Also, SOD1 protein expression was significantly (p<.05) higher in the NDEx group compared to the ND group and HFDEx group compared to the HFD group in the skeletal muscle.CONCLUSIONS: In conclusion, combine exercise intervention of high fat diet-induced obesity resulted in decreased cell repair protein and antioxidant enzyme protein in the myocardium. Therefore, it is thought that combine exercise intervention for obese induced rats improved the cell repair protein and antioxidant enzyme activity of the myocardium.
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Cardiovascular disease (CVD) is potentiated by risk factors including physical inactivity and remains a leading cause of morbidity and mortality. Although regular physical activity (PA) does not reverse atherosclerotic coronary disease, precursory exercise improves clinical outcomes in those experiencing life-threatening CVD events. Exercise preconditioning describes the cardioprotective phenotype whereby even a few exercise bouts confer short-term multifaceted protection against acute myocardial infarction. First described decades ago in animal investigations, cardioprotective mechanisms responsible for exercise preconditioning have been identified through reductionist preclinical studies, including the upregulation of endogenous antioxidant enzymes, improved calcium handling, and enhanced bioenergetic regulation during a supply-demand mismatch. Until recently, translation of this research was only inferred from clinically-directed animal models of exercise involving ischemia-reperfusion injury, and reinforced by the gene products of exercise preconditioning that are common to mammalian species. However, recent clinical investigations confirm that exercise preconditions the human heart. This discovery means that simply the initiation of a remedial exercise regimen in those with abnormal CVD risk factor profiles will provide immediate cardioprotective benefits and improved clinical outcomes following acute cardiac events. In conclusion, the prophylactic biochemical adaptations to aerobic exercise are complemented by the long-term adaptive benefits of vascular and architectural remodeling in those who adopt a physically active lifestyle.
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Background and Objectives: Diabetic patients are highly susceptible to cardiovascular involvement. Therefore, the aim of the present study was to determine the effect of six weeks of moderate-intensity endurance training on serum levels of Klotho and expression of the fibroblast-23 growth factor (FGF23) gene in the hearts of diabetic rats. Materials and Methods: In this experimental study, 21 adult male Wistar rats were randomly divided into three groups of seven: diabetic training group (DT), diabetic control group (DC), and healthy control group (HC). Diabetes was induced by intraperitoneal injection of Streptozotocin (STZ). Animals performed moderate-intensity endurance training for six weeks. Serum levels of Klotho and FGF23 gene expression in the heart tissue were evaluated by Elisa method and real time PCR, respectively. Data were analyzed by one-way analysis of variance and Scheffe’s post hoc test. Results: The findings showed that after six weeks of training, blood glucose concentration (mg/dl) in the DT group was significantly lower than the DC group (p=0.001), and serum levels of Klotho (ng/ml) were significantly increased compared to the DC (p=0.032), but there was no significant difference between the DT and DC groups in the expression of FGF23 gene (relative expression) (p=0.171). Conclusion: The results suggested that moderate-intensity endurance training has a positive effect on the serum levels of Klotho and blood glucose, and it appears to be somewhat protective of heart function. Keywords: Klotho, FGF23, Endurance training, Diabetes, Heart, Rat Funding: This study was funded by the University of Mohaghegh Ardabili. Conflict of interest: None declared. Ethical approval: The Ethics Committee of Ardabil University of Medical Sciences approved the study (IR.ARUMS.REC.1398.251). How to cite this article: Bolboli L, Khajehlandi M. The Effect of Six Weeks of Moderate-Intensity Endurance Training on Serum Levels of Klotho and Expression of the Fibroblast-23 Growth Factor Gene (FGF23) in the Hearts of Diabetic Rats: An Experimental Study. J Rafsanjan Univ Med Sci 2021; 20 (4): 371-86. [Farsi] Keywords: Klotho, FGF23, Endurance training, Diabetes, Heart, Rat
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Effect of Six Weeks of Moderate-Intensity Endurance Training on Serum Levels of Klotho and Expression of the Fibroblast-23 Growth Factor Gene (FGF23) in the Hearts of Diabetic Rats: An Experimental Study L. Bolboli1, M. Khajehlandi2 Received: 28/03/21 Sent for Revision: 24/04/21 Received Revised Manuscript: 15/05/21 Accepted: 16/05/21 Background and Objectives: Diabetic patients are highly susceptible to cardiovascular involvement. Therefore, the aim of the present study was to determine the effect of six weeks of moderate-intensity endurance training on serum levels of Klotho and expression of the fibroblast-23 growth factor (FGF23) gene in the hearts of diabetic rats. Materials and Methods: In this experimental study, 21 adult male Wistar rats were randomly divided into three groups of seven: diabetic training group (DT), diabetic control group (DC), and healthy control group (HC). Diabetes was induced by intraperitoneal injection of Streptozotocin (STZ). Animals performed moderate-intensity endurance training for six weeks. Serum levels of Klotho and FGF23 gene expression in the heart tissue were evaluated by Elisa method and real time PCR, respectively. Data were analyzed by one-way analysis of variance and Scheffe’s post hoc test. Results: The findings showed that after six weeks of training, blood glucose concentration (mg/dl) in the DT group was significantly lower than the DC group (p=0.001), and serum levels of Klotho (ng/ml) was significantly increased compared to the DC (p=0.032), but there was no significant difference between the DT and DC groups in the expression of FGF23 gene (relative expression) (p=0.171). Conclusion: The results suggested that moderate-intensity endurance training has a positive effect on the serum levels of Klotho and blood glucose, and it appears to be somewhat protective of heart function. Key words: Klotho, FGF23, Endurance training, Diabetes, Heart, Rat Funding: This study was funded by University of Mohaghegh Ardabili. Conflict of interest: None declared. Ethical approval: The Ethics Committee of Ardabil University of Medical Sciences approved the study (IR.ARUMS.REC.1398.251). How to cite this article: Bolboli L, Khajehlandi M. The Effect of Six Weeks of Moderate-Intensity Endurance Training on Serum Levels of Klotho and Expression of the Fibroblast-23 Growth Factor Gene (FGF23) in the Hearts of Diabetic Rats: An Experimental Study. J Rafsanjan Univ Med Sci 2021; 20 (4): 371-86. [Farsi] 1 - Associate Prof., Dept. of Exercise Physiology, Faculty of Educational Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil, Iran, ORCID: 0000-0002-7981-4343 (Corresponding Author) Tel: (045) 33520457, Fax: (045) 33520457, E-mail: l_bolboli@uma.ac.ir 2 - PhD Candidate, Dept. of Exercise Physiology, Faculty of Educational Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil,
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Background Aging decreases ischemic tolerance, while exercise prevents myocardial ischemia reperfusion (IR) injury. The cardioprotective role of high intensity interval training (HIIT), however, is unknown. Methods Accordingly, we investigated 8 weeks (5 days/week, 40 min/day) of HIIT treadmill exercise (60%/90% of VO2 peak) on IR injury in young (2-month) and senescent (20-month) Wistar rat myocardia (N = 10/group). Surgical IR (30 min/120 min) was performed via reversible left anterior descending artery ligation and ECG was analyzed to determine ventricular ectopy during IR period. Results Infarction size and oxidative stress were measured in hearts post-mortem. Glutathione peroxidase activity and Myeloperoxidase levels were mitigated with age, but elevated post IR. HIIT potentiated antioxidant defenses in young and old hearts, and infarction size was lower in young HIIT trained. Metrics of reactive oxygen species were not lower after IR, and were not affected by HIIT in young or old rats. Ventricular ectopy score in senescent rats was insignificantly more than young rats and HIIT significantly decreased ventricular ectopy score in young and senescent rats. Conclusions Findings indicate that IR tolerance is mitigated in senescent hearts, while HIIT ameliorated infarction by increasing antioxidant enzymes activity in young and senescent hearts.
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Myocardial disorders are the most common cause of renal failure and mortality in diabetic patients, but the molecular mechanism of this process is not yet clear. The reduction of nuclear Erythroid2-related factor-2 (Nrf-2) and positive regulators of Nrf-2 proteins, such as DJ-1 and microRNA-126 (miR-126), after hypoxia and the promotion of reactive oxygen species, might be an intervention indicator in renal failure after myocardial ischemia-reperfusion. Therefore, this study evaluates the renoprotective effect of exercise training and Crataegus persica extract (CE) on myocardial ischemia-reperfusion-induced kidney injury in diabetic rats. Fifty rats were divided into five groups: healthy sedentary control (Con), sedentary diabetic (D), interval trained diabetic (TD), diabetic plus Crataegus persica extract treatment (CD), and interval trained diabetic plus Crataegus persica extract treatment (TCD) groups. The rats in the exercise groups were subjected to moderate-intensity interval training five days per week for ten weeks. The rats in CD and TCD groups received 300 mg/kg of Crataegus persica through gavage for ten weeks. Then, the subjects underwent 30 min of myocardial ischemia and subsequently reperfusion for 24 h. At the end of the experiment, insulin sensitivity, oxidative stress, renal function, histopathology of the kidney, Nrf-2, miR-126, and DJ-1 gene expression levels were evaluated. The results show that the treatments decreased elevated levels of renal oxidative stress, glomerular filtration rate, insulin sensitivity, and pathological score in diabetic rats. Also, the expression of Nrf-2 and miR-126, unlike DJ-1, decreased in diabetic rats due to interval training. Due to the results, diabetes aggravates acute myocardial ischemia-reperfusion-induced kidney injury, while moderate-intensity interval training and Crataegus persica treatment simultaneously ameliorate myocardial ischemia-reperfusion-induced renal injury via miR-126/Nrf-2 pathway and improve insulin sensitivity and renal function in type 1 diabetic rats.
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[GRAPHICS] Palladium-mediated coupling/intramolecular indole cyclization of terminal alkynes with resin 8, followed by cleavage of the sulfonamide linkage, were executed under mild conditions to provide diverse indoles 10 in excellent yield and purity. This chemistry benefits from a dual activation process that derives from use of a traceless N-sulfonyl linker. Also, direct mercuration of 9 (X = H, R = 4-Me-C6H4), followed by palladium mediated coupling with methyl acrylate, efficiently provided I functionalized product 12.
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We examined the effects of two exercise training modalities, i.e., low-intensity endurance and sprint running, on in vitro, isovolumic myocardial performance following ischemia and reperfusion. Rats ran on a treadmill 5 d·wk-1 for 6 wk at the following levels: endurance; 20 m·min-1, 0% grade, 60 min·d-1 and sprint; five 1-min runs at 75 m·min-1, 15% grade interspersed with 1-min active recovery runs at 20 m·min-1, 15% grade. Both endurance and sprint training significantly improved exercise tolerance relative to control (P < 0.05) on two graded exercise tests. Buffer perfused hearts of control (N = 18), endurance (N = 20), and sprint(N = 13) trained animals underwent no-flow ischemia (20 min) and reperfusion (30 min) in a Langendorff mode. During reperfusion, left ventricular developed pressure and its first derivative were 20% higher in sprint (P < 0.05) than either endurance or control hearts. Left ventricular end-diastolic pressure was lowest in sprint during reperfusion(sprint, 10 ± 1 mm Hg vs endurance, 14 ± 2 mm Hg; and control, 14 ± 2 mm Hg, at 30 min reperfusion). Hearts were then used for biochemical studies or dissociated into single cells for measurement of contraction, cell calcium, and action potential duration. Single cell contractions were greatest in sprint despite similar calcium transients in all groups. Ischemia/reperfusion caused action potential prolongation in control but not trained myocytes. Hearts from sprint had the greatest glycer-aldehyde-3-phosphate dehydrogenase activity (P < 0.05) and a tendency towards increased superoxide dismutase activity. These results suggest that sprinting increases myocardial resistance to ischemia/ reperfusion. This protection may be secondary to increased myofilament calcium sensitivity and/or myocardial expression of glyceraldehyde-3-phosphate dehydrogenase.
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The aims were: (1) to determine if a new ischaemia selective ATP dependent potassium (KATP) channel antagonist, sodium 5-hydroxydecanoate (5-HD), blocks ischaemic preconditioning in dogs; (2) to determine whether a small intracoronary dose of glibenclamide, a classical sulphonylurea KATP channel antagonist, could block ischaemic preconditioning independent of systemic metabolic effects. Barbitone anaesthetised dogs were subjected to 60 min of left circumflex coronary artery occlusion followed by 5 h of reperfusion. Preconditioning was produced by a single 5 min left circumflex occlusion followed by 10 min of reperfusion prior to the 60 min occlusion period. 5-HD (150 micrograms.kg-1 x min-1) or vehicle was given by intracoronary infusion into the ischaemic region over 20 min, beginning 15 min prior to the 60 min occlusion period in the presence or absence of preconditioning. Glibenclamide (3 micrograms.kg-1 x min-1) was given by intracoronary infusion into the left circumflex artery during the 5 min preconditioning period or during the first 5 min of occlusion in preconditioned or non-preconditioned dogs. Transmural myocardial blood flow was measured by radioactive microspheres and infarct size determined by triphenyltetrazolium staining and expressed as a percent of the area at risk. There were no differences in haemodynamic variables, myocardial blood flow, area at risk, or blood glucose between groups. Infarct size was markedly reduced in preconditioned dogs compared to control animals, at 7(SEM 2)% v 29(4)%, p < 0.05 The reduction in infarct size by preconditioning was blocked completely by intracoronary 5-HD, or by intracoronary glibenclamide given during preconditioning or during the first 5 min of the prolonged occlusion period. Neither 5-HD nor glibenclamide affected infarct size in the absence of preconditioning at the doses studied. These results further strengthen the hypothesis that activation of myocardial KATP channels is involved in the mechanism of ischaemic preconditioning in dogs.
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Single or multiple brief periods of ischemia (preconditioning) have been shown to protect the myocardium from infarction after a subsequent more prolonged ischemic insult. To test the hypothesis that preconditioning is the result of opening ATP-sensitive potassium (KATP) channels, a selective KATP channel antagonist, glibenclamide, was administered before or immediately after preconditioning in barbital-anesthetized open-chest dogs subjected to 60 minutes of left circumflex coronary artery (LCX) occlusion followed by 5 hours of reperfusion. Preconditioning was elicited by 5 minutes of LCX occlusion followed by 10 minutes of reperfusion before the 60-minute occlusion period. Glibenclamide (0.3 mg/kg i.v.) or vehicle was given 10 minutes before the initial ischemic insult in each of four groups. In a fifth group, glibenclamide was administered immediately after preconditioning. In a final series (group 6), a selective potassium channel opener, RP 52891 (10 micrograms/kg bolus and 0.1 micrograms/mg/min i.v.) was started 10 minutes before occlusion and continued throughout reperfusion. Transmural myocardial blood flow was measured at 30 minutes of occlusion, and infarct size was determined by triphenyltetrazolium staining and expressed as a percent of the area at risk. There were no significant differences in hemodynamics, collateral blood flow, or area at risk between groups. The ratio of infarct size to area at risk in the control group (28 +/- 6%) was not different from the group pretreated with glibenclamide in the absence of preconditioning (31 +/- 6%). Preconditioning produced a marked reduction (p less than 0.002) in infarct size (28 +/- 6% to 6 +/- 2%), whereas glibenclamide administered before or immediately after preconditioning completely abolished the protective effect (28 +/- 6% and 30 +/- 8%, respectively). RP 52891 also produced a significant (p less than 0.03) reduction (28 +/- 6% to 13 +/- 3%) in infarct size. These results suggest that myocardial preconditioning in the canine heart is mediated by activation of KATP channels and that these channels may serve an endogenous myocardial protective role.
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Mitochondria take up and extrude various inorganic and organic ions, as well as larger substances such as proteins. The technique of patch clamping should provide real-time information on such transport and on energy transduction in oxidative phosphorylation. It has been applied to detect microscopic currents from mitochondrial membranes and conductances of ion channels in the 5-1,000 pS range in the outer and inner membranes. These pores are not, however, selective for particular ions. Here we use fused giant mitoplasts prepared from rat liver mitochondria to identify a small conductance channel highly selective for K+ in the inner mitochondrial membrane. This channel can be reversibly inactivated by ATP applied to the matrix side under inside-out patch configuration; it is also inhibited by 4-aminopyridine and by glybenclamide. The slope conductance of the unitary currents measured at negative membrane potentials was 9.7 +/- 1.0 pS (mean +/- s.d., n = 6) when the pipette solution contained 100 mM K+ and the bathing solution 33.3 mM K+. Our results indicate that mitochondria depolarize by generating a K+ conductance when ATP in the matrix is deficient.
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Both acute acetaminophen toxicity and physical exercise are accompanied by structural and functional damage to tissues. For acute acetaminophen toxicity, this damage occurs mainly in the liver. This damage, which is believed to be initially caused by oxidation and/or arylation, occurs only after depletion of liver glutathione (GSH). GSH normally protects against oxidation and/or arylation. Prolonged physical exercise also depletes GSH in the body. We hypothesized that with endurance training (repeated oxidant stress) tissues will develop mechanisms to prevent GSH depletion. Our results show that, for the same amount of submaximal exercise, trained rats are able to maintain their levels of GSH or their GSH redox status (in the liver, heart, skeletal muscle and plasma) in contrast to their untrained counterparts. Also, upon administration of acetaminophen, trained rats show a less pronounced depletion in liver GSH than untrained rats. We also hypothesized that training may lead to improved maintenance of tissue GSH homeostasis because of induction in the enzyme pathways of protection. We observe that training significantly increases (50-70%) glutathione peroxidase and reductase, glucose-6-phosphate dehydrogenase, and catalase activity in heart and skeletal muscle. Since GSH, in addition to providing cellular protection, also functions in other physiological processes including transport and metabolism, the training-induced benefits seen here may have more far-reaching consequences than ever before realized.