Fedor Simko

Comenius University Bratislava · Institute of Pathological Physiology (Faculty of Medicine)

This study investigated whether chronic isoproterenol administration could induce kidney alterations and whether ivabradine, a heart rate (HR)-reducing substance exerting cardiovascular protection, is able to attenuate potential kidney damage. Twenty-eight Wistar rats were divided into non-diseased controls, rats treated with ivabradine, rats treat...

Anxiety disorders are the most common mental diseases. Anxiety and the associated physical symptoms may disturb social and occupational life and increase the risk of somatic diseases. The pathophysiology of anxiety development is complex and involves alterations in stress hormone production, neurosignaling pathways or free radical production. The v...

Lactacystin is a specific proteasome inhibitor that blocks the hydrolysis of intracellular proteins by ubiquitin/proteasome system inhibition. The administration of lactacystin to rats induced hypertension and remodeling of the left ventricle and aorta. This study tested whether lactacystin induces structural and fibrotic rebuilding of the kidneys...

This study investigated whether sacubitril/valsartan and ivabradine are able to prevent left ventricular (LV) fibrotic remodelling and dysfunction in a rat experimental model of spontaneous hypertension (spontaneously hypertensive rats, SHRs) and whether this potential protection is associated with RAAS alterations. Five groups of three-month-old m...

The number of poorly controlled hypertensive patients worldwide is alarmingly high, and the introduction of antihypertensive drugs with principally novel mechanisms of action is not anticipated. Instead, better adherence to treatment, fixed antihypertensive drug combinations and careful self-monitoring are recommended. However, the chronotherapeuti...

Background: Matrix metalloproteinase-9 (MMP-9) is crucial in tissue remodeling after an adverse cardiac event. In experimental studies, melatonin has been found to attenuate MMP-9 activation. The present study assessed the effects of systemic melatonin administration on the prognosis of patients with acute myocardial infarction (AMI) successfully...

Besides acute respiratory distress syndrome, acute cardiac injury is a major complication in severe coronavirus disease 2019 (COVID-19) and associates with a poor clinical outcome. Acute cardiac injury with COVID-19 can be of various etiologies, including myocardial ischemia or infarction and myocarditis, and may compromise cardiac function, result...

No single treatment will eliminate the COVID-19 pandemic. It is imperative that all available tactics and medications be used to overcome this disease, although it will probably never totally disappear. Melatonin is inexpensive so it is affordable throughout the world, it does not require refrigeration and it has a very long shelf-life. Melatonin h...

Numerous pharmaceutical drugs have been repurposed for use as treatments for COVID-19 disease. These drugs have not consistently demonstrated high efficacy in preventing or treating this serious condition and all have side effects to differing degrees. We encourage the continued consideration of the use of the antioxidant and anti-inflammatory agen...

Besides the well-recognized risk factors, novel conditions increasing cardiovascular morbidity and mortality are emerging. Undesirable emotions and behavior such as anxiety and depression, appear to participate in worsening cardiovascular pathologies. On the other hand, deteriorating conditions of the heart and vasculature result in disturbed menta...

Experimental and clinical studies from recent decades provided evidence supporting the hypothesis that the heart’s endocrine function is part of the neurohumoral network. The natriuretic peptide system consists of hormones generated by the myocardium having similar cardioprotective effects involved in cardiovascular homeostasis. During hemodynamic...

Arterial blood pressure (BP) undergoes variable changes over 24 hours conforming to physiological daily rhythms. Disruption of the natural BP circadian rhythm is associated with worsened cardiovascular disease (CVD) prognosis. Increased nocturnal BP or at least insufficient BP decline at night, i.e. non-dipping, may be associated with morphological...

Non-dipping heart rate (HR), i.e., HR decline overnight by <10% of the daytime mean, is coupled with an increased risk of adverse outcomes in the general population and various cardiovascular pathologies. Although sustained sympathetic over-activation at night is considered to be pivotal in the pathophysiology of non-dipping HR, other factors may a...

Current knowledge on the renin–angiotensin system (RAS) indicates its central role in the pathogenesis of cardiovascular remodelling via both hemodynamic alterations and direct growth and the proliferation effects of angiotensin II or aldosterone resulting in the hypertrophy of cardiomyocytes, the proliferation of fibroblasts, and inflammatory immu...

Angiotensin-converting enzyme 2 (ACE2) is the leading player of the protective renin-angiotensin system (RAS) pathway but also the entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RAS inhibitors seemed to interfere with the ACE2 receptor, and their safety was addressed in COVID-19 patients. Pedrosa et al. (Clin. Sci....

Despite advances in heart failure (HF) pharmacotherapy over the last three decades, the residual mortality with HF remains high. The antipode to the drug-induced inhibition of vasoconstrictive and proliferative substances could be an increase of vasodilative and antiproliferative humoral substances, including the natriuretic peptides (NPs). NPs are...

The renin–angiotensin–aldosterone system (RAAS) ranks among the most challenging puzzles in cardiovascular medicine [...]

Elevated heart rate (HR) is a well-recognized but somewhat neglected risk factor among the healthy population and various cardiovascular pathologies. High HR is fraught with a spate of detrimental cardiovascular consequences including immense myocardial oxygen demand in reduced diastolic perfusion time and low, oscillatory vascular shear stress wit...

Acute respiratory distress syndrome (ARDS) is characterized by massive inflammation, increased vascular permeability and pulmonary edema. Mortality due to ARDS remains very high and even in the case of survival, acute lung injury can lead to pulmonary fibrosis. The renin–angiotensin system (RAS) plays a significant role in these processes. The acti...

This study investigated whether ivabradine, a selective If current inhibitor reducing heart rate (HR), is able to improve survival and prevent left ventricular (LV) remodeling in isoproterenol‐induced heart damage. Wistar rats were treated for 6 weeks: controls (n = 10), ivabradine (10 mg/kg/day orally; n = 10), isoproterenol (5 mg/kg/day intraperi...

Hypertension-induced renal injury is characterized by structural kidney alterations and function deterioration. Therapeutics for kidney protection are limited, thus novel renoprotectives in hypertension are being continuously sought out. Ivabradine, an inhibitor of the I f current in the sinoatrial node reducing heart rate (HR), was shown to be of...

Renin-angiotensin system (RAS) inhibition supposedly increases the expression of angiotensin converting enzyme 2, serving as a binding site for SARS-CoV-2. Concerns arose regarding therapy with RAS inhibition during the COVID-19 pandemic. However, the pharmacological restraining the classical RAS axis might be beneficial due to the reduction of del...

Increased concentration of uric acid (UA) is positively associated with the clinical severity but negatively associated with the prognosis of heart failure (HF). However, data related to the association between UA concentration and N-terminal pro brain natriuretic peptide (NT-proBNP) are still lacking. The aim of the study was to analyze the relati...

Ivabradine decreases heart rate by selective inhibition of the If current in the sinoatrial node. Ivabradine is declared to have no direct effect on the autonomic nervous system (ANS). However, there are some data suggesting an (at least indirect) effect of ivabradine on the ANS. The pathomechanism behind is unclear. Based on the complex of plexuse...

Chronotherapy is a therapeutic approach that respects the circadian variations of physiological processes. The chronotherapeutic approach to hypertension has been shown to improve blood pressure (BP) control and reduce cardiovascular events. Chronotherapy might be of similar importance in the treatment of elevated heart rate (HR). The 2016 statemen...

This study investigated the effect of lisinopril (angiotensin-converting enzyme inhibi-tor) on potential behavioural alterations in spontaneously hypertensive rats (SHR). Three groups of 15-17-week-old rats were investigated for 2 weeks: Wistar control group, SHR group and SHR+lisinopril group. Systolic blood pressure (SBP) was normal in Wistar rat...

We hypothesised that decreasing elevated night‐time heart rate (HR) in hypertension by administering a bradycardic agent (ivabradine) at bedtime could bring cardiovascular benefit. Since rats are nocturnal animals, they exhibit circadian rhythms phase‐shifted relative to humans. Sixty‐six Wistar rats were divided into nondiseased controls and rats...

There is a great urgency of detecting and monitoring myocardial fibrosis in clinical practice with the aim to improve and personalize therapy against cardiac remodelling. Hence, the aim of this study was to describe alterations in and show potential correlations between the structural characteristics and the molecular and biochemical markers of car...

Cardiovascular pathologies are frequently associated with anxiety and other behavioral disturbances. Ivabradine, an inhibitor of the hyperpolarization-activated cyclic nucleotide-gated channels in the sinoatrial node, decreases heart rate and provides cardiovascular protection. Although ivabradine is increasingly used in cardiovascular medicine, th...

Ivabradine, the selective inhibitor of the If current in the sinoatrial node, exerts cardiovascular protection by its bradycardic effect and potentially pleiotropic actions. However, there is a shortage of data regarding ivabradine’s interaction with the renin-angiotensin-aldosterone system (RAAS). This study investigated whether ivabradine is able...

This study investigated whether continuous light exposure (CLE) results in behavioural disturbances in rats and whether melatonin can modify these potential changes. Four groups of 3-month-old Wistar rats were treated as follows for six weeks: control, melatonin, CLE, and CLE with melatonin. CLE increased systolic blood pressure and melatonin reduc...

No data are available on heart function in chronic testosterone deficiency and on the effect of estrogen treatment. Eighteen 4-week-old male Lewis rats were randomly divided into three groups (n = 6): one group of sham-operated rats and two groups of castrated rats. 66 weeks after surgery, one castrated group received a dose of 17β-estradiol (10 μg...

Personalized medicine is partly based on biomarker-guided diagnostics, therapy and prognosis, which is becoming an unavoidable concept in modern cardiology. However, the clinical significance of single biomarker studies is rather limited. A promising novel approach involves combining multiple markers into a multiplex panel, which could refine the m...

The renin-angiotensin-aldosterone system (RAAS) is a dominant player in several cardiovascular pathologies. This study investigated whether alterations induced by l-NAME, (NLG)-nitro-l-arginine methyl ester, a nitric oxide synthase inhibitor, and the protective effect of melatonin are associated with changes in the RAAS. Four groups of 3-month-old...

Mitochondrial Cardiology is part of Mitochondrial Medicine, which provides a comprehensive view of mitochondrial disturbances in terms of clinical, metabolic, genetic and pathological information relevant to the diagnosis and treatment of mitochondrial diseases. Mitochondrial Cardiology highlights the irreplaceable importance of mitochondria in hea...

Abstrakt: Aims: The mutual interrelation between cardiovascular diseases and anxiety disorder has been frequently discussed. The aim of this study was to show whether L-NAME (N[omega]-nitro-L-arginine methyl ester)-induced hypertension could induce behavioural disturbances in rats and whether these potential disorders could be modified by chronic t...

Background Body weight changes are associated with significant variations in blood pressure (BP). Body mass modifications may, therefore, influence hypertension control in primary care. Methods Patients with a history of essential arterial hypertension were observed for 12 months. Anthropometric data and clinical BP were evaluated at the time of t...

Introduction: The control of hypertension and the resulting cardiovascular events is still insufficient. Thus, the search for novel means for blood pressure (BP) reduction remains worth further clinical and research attention. The advances in vector and construct design sketch the use of gene therapy in hypertension. Areas covered: The authors have...

Lactacystin is a proteasome inhibitor that interferes with several factors involved in heart remodelling. The aim of this study was to investigate whether the chronic administration of lactacystin induces hypertension and heart remodelling and whether these changes can be modified by captopril or melatonin. In addition, the lactacystin-model was co...

Cardiovascular diseases including hypertension are often associated with behavioural alterations. The aim of this study was to show, whether ivabradine, the blocker of If-channel in sinoatrial node, is able to modify the behaviour of rats in L-nitro-arginine methyl ester (L-NAME)-induced hypertension and to compare the effect of ivabradine with cap...

The renin-angiotensin system (RAS) plays a crucial role in cardiovascular regulations and its modulation is a challenging target for the vast majority of cardioprotective strategies. However, many biological effects of these drugs cannot be explained by the known mode of action. Our comprehension of the RAS is thus far from complete. The RAS repres...

Elevated heart rate is a risk factor for cardiovascular and all-cause mortalities in the general population and various cardiovascular pathologies. Insufficient heart rate decline during the night, that is, nondipping heart rate, also increases cardiovascular risk. Abnormal heart rate reflects an autonomic nervous system imbalance in terms of relat...

Tn is a unique translational biomarker in cardiology whose potential has not been diminished in the new era of high sensitive assays. cTns can be valuable markers in cardiac diseases as well as in infectious diseases and respiratory diseases. Furthermore, the role of cTns is growing in the routine evaluation of cardioxicity and in determining the e...

Hyperuricaemia represents nowaday the new risk factor for cardiovascular diseases. Prevalence data and its treatment in our patient´s population are still missing. Literature data shows, that its prevalence differs in various populations significantly from 4 % up to 40 % with race and geographical means. In the hospital population its prevalence is...

Microparticles represent the complex of vesicular structures originating from plasmatic membranes of endothelial cells, thrombocytes, erythrocytes, mono-cytes or myofibroblasts. They are released from the daughter cells under various physiological and pathological circumstances in the process of cellular activation, apopthosis and/or damage. Among...

The dysbalance between the sympathetic and parasympathetic vegetative system and increased free radical burden in the central nervous system (CNS) are the important pathophysiological disorders and therapeutic targets in hypertension. Besides the effects on cardiovascular system, the pineal hormone, melatonin (N-acetyl-5-methoxytryptamine) may exer...

Hyperuricaemia represents nowaday the new risk factor for cardiovascular diseases. Prevalence data and its treatment in our patient's population are still missing. Literature data shows, that its prevalence differs in various populations significantly from 4% up to 40% with race and geographical means. In the hospital population its prevalence is a...

N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a ubiquitous molecule generated in all mammalian tissues from the N-terminal sequence of thymosin β4 (Tβ4) by the action of propyl oligopeptidase. Ac-SDKP is an alternative substrate for angiotensin converting enzyme (ACE). There are several indications that Ac-SDKP may be protective in the cardiov...

Cardiac troponins (cTns) seem to be more sensitive for the detection of anthracycline cardiotoxicity than the currently recommended method of monitoring LV systolic function. However, the optimal timing of blood sampling remains unknown. Hence, the aims of the present study were to determine the precise diagnostic window for cTns during the develop...

Arterial hypertension is the most prevalent controllable disease world-wide. Yet, we still need to further improve blood pressure control, deal with resistant hypertension, and we hope to reduce risk "beyond blood pressure." The number of candidate molecules aspiring for these aims is constantly declining. The new possible approaches to combat high...

Unlabelled: Hyperuricaemia represents nowaday the new risk factor for cardiovascular diseases. Prevalence data and its treatment in our patient´s population are still missing. Literature data shows, that its prevalence differs in various populations significantly from 4 % up to 40 % with race and geographical means. In the hospital population its...

The pineal hormone, melatonin (N-acetyl-5-methoxytryptamine), shows potent receptor-dependent and -independent actions, which participate in blood pressure regulation. The antihypertensive effect of melatonin was demonstrated in experimental and clinical hypertension. Receptor-dependent effects are mediated predominantly through MT1 and MT2 G-prote...

Chronic kidney disease (CKD) is a serious public health problem. Current therapies are designed to slow down progression of the disease and avoid the necessity of dialysis or kidney transplantation. CKD is characterized by chronic inflammation and progressive cell death resulting in fibrotic rebuilding of renal tissue. Melatonin, the primary produc...

Exposure of rats to continuous light attenuates melatonin production and results in hypertension development. This study investigated whether hypertension induced by continuous light (24 hours/day) exposure induces heart and aorta remodelling and if these alterations are prevented by melatonin or angiotensin converting enzyme inhibitor captopril. F...

Melatonin was previously shown to reduce blood pressure and left ventricular remodeling in several models of experimental heart damage. This study investigated whether melatonin prevents left ventricular (LV) remodeling and improves survival in isoproterenol-induced heart failure. In the first experiment, four groups of 3-month old male Wistar rats...

Chronic continuous light exposure leads to melatonin deficiency along with complex neurohumoral activation resulting in hypertension development in rats. The aim of this study was to show, whether continuous light induces fibrotic rebuilding of the aorta and whether the treatment with melatonin or angiotensin converting enzyme inhibitor captopril c...

Chronic kidney disease (CKD) represents a serious public health problem with increasing prevalence and novel approaches to renal protection are continuously under investigation. The aim of this study was to compare the effect of melatonin and angiotensin II type 2 receptor agonist compound 21 (C21) to angiotensin converting enzyme inhibitor captopr...

The multimarker approach using Luminex technology represents a new tool for studying the pathogenesis of cardiovascular disease. Although many cardiac biomarkers in heart failure have been well established, the role and significance of their measurement in hypertensive patients is still questionable. The aim of our study was to evaluate the relatio...

Melatonin secreted by the pineal gland plays an important role in the regulation of blood pressure (BP) and its administration reduces hypertension both in animals and humans. There are two experimental models of melatonin-deficient hypertension: one induced by pinealectomy and another by continuous 24 hour exposure to light. Both models cause mela...

Introduction: Melatonin synchronizes circadian rhythms with light/dark period and it was demonstrated to correct chronodisruption. Several melatonin receptor agonists with improved pharmacokinetics or increased receptor affinity are being developed, three of them are already in clinical use. However, the actions of melatonin extend beyond chronobi...

Eur J Clin Invest 2012; 42 (11): 1252–1254

Type 2 diabetes mellitus is characterised by the presence of macrovascular and microvascular complications which are already present in the early stages of manifest disease. Clinically they lead to enhanced atherosclerosis and atherothrombosis (i.e. coronary heart disease, stroke, or peripheral arterial disease). Patients with type 2 diabetes melli...

Left ventricular hypertrophy (LVH), despite its adaptive nature, increases cardiovascular morbidity and mortality. Novel approaches for protection against pathological heart remodelling are presented in this supplement. Melatonin diminishes myocardial fibrosis in rats exposed to continuous light and N-nitro-L-arginine-methyl ester (L-NAME) treatmen...

Blood pressure enhancement induced by continuous light exposure represents an attractive but rarely investigated model of experimental hypertension. The aim of this study was to show whether the combination of continuous light (24 h/day) exposure and chronic N-nitro-L-arginine-methyl ester (L-NAME) treatment induces remodelling of the left ventricl...

Melatonin is suggested to be beneficial in several pathological conditions including arterial hypertension. One of the mechanisms proposed for its antihypertensive action is the protection against endothelial dysfunction. We investigated whether melatonin can accelerate the recovery from N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced hypertens...

Hypertrophy of the myocardium is induced by haemodynamic and humoral alterations, which in turn stimulate the production of factors triggering protein synthesis, thus initiating myocardial growth. It has recently been documented that nuclear factor kappa B (NF-kappaB) represents a key factor that mediates both neurohormonal and proinflammatory sign...

We aimed to analyze effects of nuclear factor-kappa B (NF-kappaB) inhibition on blood pressure (BP) regulation and cardiovascular remodelling. Adult 12-week-old male Wistar Kyoto rats (WKY) were treated with the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 40 mg/kg/day) for seven weeks. From the fourth week of L...