Jaume Padilla

• University of Missouri

RECK (Reversion-inducing Cysteine-rich Protein with Kazal Motifs) is a known negative regulator of matrix metalloproteinases (MMPs), which play a key role in extracellular matrix (ECM) degradation and vascular remodeling. Abdominal aortic aneurysm (AAA) is a devastating vascular disease characterized by the permanent localized dilation of the abdom...

Objective In conduit arteries, aging and hypertension are associated with stiffening characterized by increased cytoskeletal F‐actin and endothelial dysfunction. Herein, we determined if this also happens at the level of the resistance vasculature. Methods We retrospectively compared the mechanical and structural characteristics of small arteries...

The Lim Kinase (LIMK) family of serine/threonine kinases is comprised of LIMK1 and LIMK2, which are central regulators of cytoskeletal dynamics via their well-characterized roles in promoting actin polymerization and destabilizing the cellular microtubular network. The LIMKs have been demonstrated to modulate several fundamental physiological proce...

Insulin has important vasodilatory effects in the peripheral circulation, but less is known about insulin's role in cerebrovascular control. Herein, we hypothesized both systemic (intravenous) and local (intranasal) insulin administration would increase indices of cerebral blood flow and reduce cerebrovascular compliance (Ci) in young adults. Parti...

Degradation of the endothelial glycocalyx in type 2 diabetes (T2D) is thought to contribute to impaired shear stress mechanotransduction, leading to endothelial dysfunction and the development of cardiovascular disease. Herein, we tested the hypothesis that restoration of the endothelial glycocalyx with dietary supplementation of glycocalyx precurs...

The lining of blood vessels is constantly exposed to mechanical forces exerted by blood flow against the endothelium. Endothelial cells detect these tangential forces ( i.e., shear stress), initiating a host of intracellular signaling cascades that regulate vascular physiology. Thus, vascular health is tethered to the endothelial cells' capacity to...

Systemic insulin increases muscle sympathetic nerve activity (MSNA) via both central actions within the brainstem and peripheral activation of the arterial baroreflex. Augmented MSNA during hyperinsulinemia likely restrains peripheral vasodilation and contributes to the maintenance of blood pressure (BP). However, in the absence of insulin action w...

Vascular smooth muscle cells (VSMCs) are exposed to a wide range of mechanical stimuli in both physiological and pathological conditions. These mechanical stimuli are converted into biochemical signals that regulate VSMC contractility and cytoskeletal structures in a process known as mechanotransduction. Thus, the ability of VSMCs to sense and resp...

Endothelial dysfunction represents a causal factor in the pathogenesis of cardiovascular disease associated with type 2 diabetes (T2D), including hypertension. Previous work has revealed that endothelial mechanosensing structures are degraded in T2D, resulting in impaired shear stress mechanotransduction and decreased flow-mediated dilation (FMD)....

Although arterial stiffening undeniably contributes to cardiovascular disease, the cellular and molecular mechanisms leading to increased arterial stiffness are not well understood. Increased arterial stiffness in disease states such as obesity and type 2 diabetes typically coexists with indices of endothelial dysfunction including diminished nitri...

Type 2 diabetes (T2D) is a major risk factor for cardiovascular disease (CVD) development and associated mortality. In the cerebral circulation, T2D-related vascular disfunction also contributes to diverse cerebrovascular diseases including stroke, cognitive impairment, and dementia. Previous research has documented that endothelial dysfunction and...

Introduction: Intermittent hypoxia (IH) is a phenomenon observed with obstructive sleep apnea (OSA), which is highly prevalent in patients with abdominal aortic aneurysm (AAA). However, it remains unknown if IH is a risk factor for the development of AAA. The goal of this study was to determine the effects of IH exposure on arterial stiffness, and...

Increased sitting time, the most common form of sedentary behavior, is an independent risk factor for all-cause and cardiovascular disease mortality; however, the mechanisms linking sitting to cardiovascular risk remain largely elusive. Studies over the last decade have led to the concept that excessive time spent in the sitting position, and the e...

Endothelial insulin resistance represents a causal factor in the pathogenesis of type 2 diabetes (T2D) and vascular disease, thus the need to identify molecular mechanisms underlying defects in endothelial insulin signaling. We previously have shown that a disintegrin and metalloproteinase-17 (ADAM17) is increased while insulin receptor α-subunit (...

Neuraminidases cleave sialic acids from glycocalyx structures and plasma neuraminidase activity is elevated in type 2 diabetes (T2D). Therefore, we hypothesize circulating neuraminidase degrades the endothelial glycocalyx and diminishes flow-mediated dilation (FMD), while its inhibition restores shear mechanosensation and endothelial function in T2...

Patients with type 2 diabetes (T2D) have an increased incidence of cardiovascular disease (CVD) morbidity and mortality. Indeed, CVD is the primary cause of death in T2D. Arterial stiffness and hypertension are both implicated in the progression of CVD in T2D. Moreover, arterial stiffening is posited to precede the development of hypertension and i...

Arterial stiffening and endothelial dysfunction are key contributors to the development and progression of cardiovascular disease (CVD) in women with obesity. Estrogen actions in the vasculature, mainly mediated via estrogen receptor alpha (ERα), result in enhanced endothelial function, lowered arterial stiffness and decreased blood pressure. Howev...

Arterial stiffening is a major risk factor for cardiovascular disease development and progression. Both hypertension and aging are associated with presence of microcirculation endothelial dysfunction, hypercontractility, and vascular stiffening. Reports suggest that while hypertension results in inward remodeling, aging is associated with either no...

Type 2 diabetes is associated with endothelial stiffening, which precedes the development of increased arterial stiffness. The role of endothelial cell stiffening in the pathogenesis of vascular disease is increasingly recognized. Indeed, evidence exists that cellular pathways that result in polymerization of endothelial cell actin filaments (F-act...

Objective: Cerebral blood flow is highly regulated and cerebrovascular responsiveness to vasodilatory stimuli is predictive of brain health. In preclinical animal models, insulin elicits cerebrovascular dilation and subsequent increases in cerebral blood flow. Contrary to this, preliminary data from our group in a large cohort of healthy humans ind...

The vascular glycocalyx, in particular, that which protrudes from the endothelium into the vascular lumen, is an important player in multiple functions of blood vessels. The glycocalyx is a mesh of glycoproteins and proteoglycans present on the outer layer of the cellular plasmalemma. In endothelial cells, the glycocalyx participates in the process...

In type 2 diabetes (T2D), endothelial dysfunction and arterial stiffening play a significant role in the development of cardiovascular disease. A central mediator of vascular dysfunction is degradation of the endothelial glycocalyx, a semipermeable mechanosensitive structure that separates the endothelium from the flow of blood and shear forces ass...

Endothelial insulin resistance represents a causal factor in the pathogenesis of type 2 diabetes (T2D) and vascular disease, thus underscoring the need to identify molecular mechanisms underlying defects in endothelial insulin signaling. We previously showed that a disintegrin and metalloproteinase-17 (ADAM17) is increased while insulin receptor α-...

Plasma neuraminidase (Neu) activity has been shown to be increased in type 2 diabetes (T2D). The net result of neuraminidase activity is cleavage of sialic acid moieties from structures such as the glycoproteins and proteoglycans found in the glycocalyx, a mesh protruding out from the plasmalemma of all cells. In the vasculature, the glycocalyx par...

Objective: Adults with obesity and insulin resistance exhibit impaired cerebrovascular reactivity and endothelial dysfunction, which increases the risk of dementia and Alzheimer’s disease. Impairments in cerebrovascular health have been attributed to vascular insulin resistance and emerging data support the use of intranasal insulin as a potential...

Objective: Systemic insulin increases muscle sympathetic nervous system activity (MSNA) via both central actions within the brainstem and peripheral activation of the arterial baroreflex. Augmented MSNA during hyperinsulinemia likely restrains peripheral vasodilation and contributes to the maintenance of blood pressure (BP). However, in the absence...

Background: Insulin-stimulated blood flow plays a key role in glucose and insulin delivery to target tissues, such as skeletal muscle. With the development of obesity and type 2 diabetes (T2D), there are impairments in vascular insulin signaling and, consequently, blunting of insulin-induced vasodilation. However, it remains unknown if diet-induced...

Endothelial dysfunction and arterial stiffening are consistently manifested in type 2 diabetes (T2D) and contribute to the development of cardiovascular disease. Consequently, there is an urgent need to identify novel therapies that improve endothelial function and reduce arterial stiffness in T2D. Endothelial dysfunction is characterized by a redu...

Introduction: Although men have a greater incidence of abdominal aortic aneurysm (AAA) compared with women, the role of sex-hormones in mediating these differences is not well understood. Given the known effect of estrogen receptor alpha (ERα) signaling in maintaining vascular wall homeostasis, the present study examines its role in the pathogenesi...

Insulin acts centrally to stimulate sympathetic vasoconstrictor outflow to skeletal muscle and peripherally to promote vasodilation. Given these divergent actions, the 'net effect' of insulin on the transduction of muscle sympathetic nerve activity (MSNA) into vasoconstriction and thus, blood pressure (BP) remains unclear. We hypothesized that symp...

Vascular insulin resistance, a major characteristic of obesity and type 2 diabetes (T2D), 47 manifests with blunting of insulin-induced vasodilation. While there is evidence that females 48 are more whole-body insulin sensitive than males in the healthy state, whether sex differences 49 exist in vascular insulin sensitivity is unclear. Also uncerta...

Vascular insulin resistance, a major characteristic of obesity and type 2 diabetes (T2D), manifests with blunting of insulin-induced vasodilation. While there is evidence that females are more whole-body insulin sensitive than males in the healthy state, whether sex differences exist in vascular insulin sensitivity is unclear. Also uncertain is whe...

Insulin resistance in the vasculature is a hallmark of type 2 diabetes (T2D) and blunting of insulin-induced vasodilation is its primary consequence. Individuals with T2D exhibit a marked impairment in insulin-induced dilation in resistance arteries across vascular beds. Importantly, reduced insulin-stimulated vasodilation and blood flow to skeleta...

Myogenic and flow-induced reactivity contribute to cerebral autoregulation, with potentially divergent roles for smaller vs. larger arteries. The present study tested the hypotheses that compared to first order (1A) branches of the middle cerebral artery, second and third order branches (2A and 3A, respectively) would exhibit greater myogenic react...

The glycocalyx is a polysaccharide structure that protrudes from the body of a cell. It is primarily conformed of glycoproteins and proteoglycans, which provide communication, electrostatic charge, ionic buffering, permeability, and mechanosensation‐mechanotransduction capabilities to cells. In blood vessels, the endothelial glycocalyx that project...

White adipose tissue (WAT) dysfunction independently predicts cardiometabolic disease, yet there is a lack of effective adipocyte-targeting therapeutics. B3AR agonists enhance adipocyte mitochondrial function and hold potential in this regard. Based on enhanced sensitivity to B3AR-mediated browning in estrogen receptor (ER)alpha-null mice, we hypot...

Inflammation and vascular insulin resistance are hallmarks of type 2 diabetes (T2D). However, the specific mechanisms that cause abnormal endothelial insulin signaling in T2D remain largely unknown. Evidence indicates that the activity of ADAM17 (a disintegrin and metalloproteinase-17) and the presence of insulin receptor (IR) in plasma are increas...

Vascular insulin resistance is a feature of obesity and type 2 diabetes that contributes to the genesis of vascular disease and glycemic dysregulation. Data from preclinical models indicate that vascular insulin resistance is an early event in the disease course preceding the development of insulin resistance in metabolically-active tissues. Whethe...

The glycocalyx is a polysaccharide structure that protrudes from the body of a cell. It is primarily conformed of glycoproteins and proteoglycans, which provide communication, electrostatic charge, ionic buffering, permeability, and mechanosensation-mechanotransduction capabilities to cells. In blood vessels, the endothelial glycocalyx that project...

Study objectives Obstructive sleep apnea (OSA) is a chronic condition characterized by intermittent hypoxia (IH) that is implicated in an increased risk of cardiovascular disease (i.e., coronary heart disease, CHD) and associated with increased overall and cardiac-specific mortality. Accordingly, we tested the hypothesis that experimental IH progre...

Objective: Hyperinsulinemia elicits an increase sympathetic nervous system activity directed toward skeletal muscle (muscle sympathetic nerve activity, MSNA). The insulin-mediated increase in MSNA is primarily attributed to its effect within the central nervous system. In addition to direct central effects, insulin also elicits peripheral vasodila...

Objective: Hyperinsulinemia has marked vasodilatory effects within the skeletal muscle vasculature in healthy young adults; however, the magnitude of insulin-stimulated cerebrovascular vasodilation is less clear. Differences between circulations may be due to a greater importance of the cerebral circulation to maintain a constant level of blood fl...

Adropin is a peptide primarily expressed and secreted by the liver and is known to regulate energy homeostasis. Increasing evidence also indicates that adropin can exert vascular effects and its low circulating levels are associated with increased arterial stiffness, obesity, and type 2 diabetes. However, whether reduced adropin contributes to arte...

Introduction: Intermittent hypoxia (IH) is one of the hallmarks of obstructive sleep apnea (OSA). OSA is highly prevalent among patients with abdominal aortic aneurysm (AAA). However, it remains unknown whether IH is a risk factor for the development and faster expansion of AAA. The goal of this study was to determine whether exposure to chronic I...

Introduction: The La ribonucleoprotein 6 (LARP6), an RNA binding protein, increases type I collagen expression by regulating mRNA stability and translation. This is mediated via its interaction with the 5' stem loop (5'SL) structure in collagen I mRNA. Disrupting this interaction by mutating the 5'SL region has been shown to reduce fibrotic remode...

45 Impaired endothelial insulin signaling and consequent blunting of insulin-induced 46 vasodilation is a feature of type 2 diabetes (T2D) that contributes to vascular disease 47 and glycemic dysregulation. However, the molecular mechanisms underlying 48 endothelial insulin resistance remain poorly known. Herein, we tested the hypothesis 49 that en...

Aging of the vasculature is characterized by endothelial dysfunction and arterial stiffening, two key events in the pathogenesis of cardiovascular disease (CVD). Treatment with sodium glucose transporter 2 (SGLT2) inhibitors is now known to decrease cardiovascular morbidity and mortality in type 2 diabetes. However, whether SGLT2 inhibition attenua...

Purpose of Review Herein, we summarize recent advances which provide new insights into the role of the autonomic nervous system in the control of blood flow and blood pressure during hyperinsulinemia. We also highlight remaining gaps in knowledge as it pertains to the translation of findings to relevant human chronic conditions such as obesity, ins...

Muscle sympathetic nerve activity (MSNA) increases during hyperinsulinemia, primarily attributed to central nervous system effects. Whether peripheral vasodilation induced by insulin further contributes to increased MSNA via arterial baroreflex-mediated mechanisms requires further investigation. Accordingly, we examined baroreflex modulation of the...

Skeletal muscle insulin resistance is a hallmark of individuals with type 2 diabetes mellitus (T2D). In healthy individuals insulin stimulates vasodilation, which is markedly blunted in T2D; however, the mechanism(s) remain incompletely understood. Investigations in rodents indicate augmented endothelin-1 (ET-1) action as a major contributor. Human...

Consumption of diets high in fat, sugar and salt (Western diet, WD) is associated with accelerated arterial stiffening, a major independent risk factor for cardiovascular disease (CVD). Obese women are more prone to develop arterial stiffening leading to more frequent and severe CVD compared to men. As tissue transglutaminase (TG2) has been implica...

Introduction: Coronavirus disease 2019 (COVID-19) has become one of the more dramatic health problems in the century. This disease has enormous consequence for the health care worldwide. In addition to high mortality rate, patients recovered from COVID-19 present short and long-term cardiovascular sequelae including chest pain, myocardial dysfuncti...

Arterial stiffening, a characteristic feature of type 2 diabetes, is an important contributor to the development and progression of cardiovascular disease (CVD). Thus, a better understanding of the precipitating factors underlying arterial stiffening is vital to identify newer targets and strategies to reduce CVD burden, particularly in diabetic wo...

Arterial stiffening, a characteristic feature of obesity and type 2 diabetes, contributes to the development and progression of cardiovascular diseases (CVD). Currently, no effective prophylaxis or therapeutics is available to prevent or treat arterial stiffening. A better understanding of the molecular mechanisms underlying arterial stiffening is...

Objective Studies have shown that fidgeting augments metabolic demand and increases blood flow to the moving limbs, whereas prolonged sitting suppresses these factors and exacerbates postprandial glucose excursions. Therefore, the hypothesis of this study was that leg fidgeting during prolonged sitting would improve postprandial glycemic control....

Beige adipocyte mitochondria contribute to thermogenesis by uncoupling and by ATP-consuming futile cycles. Since uncoupling may inhibit ATP synthesis, it is expected that expenditure through ATP synthesis is segregated to a disparate population of mitochondria. Recent studies in mouse brown adipocytes identified peridroplet mitochondria (PDM) as ha...

Individuals with heart failure (HF) frequently present with comorbidities, including obesity, insulin resistance, hypertension, and dyslipidemia. Many patients with HF experience cardiogenic dementia, yet the pathophysiology of this disease remains poorly understood. Using a swine model of cardiometabolic HF (Western diet+aortic banding; WD-AB), we...

Background Adropin is a peptide hormone that promotes nitric oxide (NO) production via activation of endothelial NO synthase (eNOS) in endothelial cells. Its circulating levels are reduced with aging and increased with aerobic exercise training (AT). Using a mouse model, we hypothesized that AT restores aging‐associated reductions in arterial and c...

Estrogen receptor β (ERb), one of the two major estrogen receptors, acts via genomic and non-genomic signaling pathways to affect many metabolic functions, including mitochondrial biogenesis and respiration. This study assessed the effect of ERb classical genomic activity on adipocyte-specific and -systemic metabolic responses to wheel running exer...

Herein we report in a sample of healthy young men (n=14) and women (n=12) that hyperinsulinemia induces time-dependent decreases in total peripheral resistance and its contribution to the maintenance of blood pressure. In the same participants, we observe profound vasodilatory effects of insulin in the lower limb despite concomitant activation of t...

Estrogen receptor  (ERb), one of the two major estrogen receptors, acts via genomic and non-genomic signaling pathways to affect many metabolic functions, including mitochondrial biogenesis and respiration. This study assessed the effect of ERb classical genomic activity on adipocyte-specific and systemic metabolic responses to wheel running exerc...

Enhanced mineralocorticoid receptor (MR) signaling is critical to the development of endothelial dysfunction and arterial stiffening. However, there is a lack of knowledge about the role of MR-induced adipose tissue inflammation in the genesis of vascular dysfunction in women. In this study, we hypothesize that MR activation in myeloid cells contri...

Estrogen receptor-α knockout (ERKO) in female, but not male, mice results in an impaired osteogenic response to exercise, but the mechanisms behind this ability in males are unknown. We explored the main and interactive effects of ERKO and exercise on cortical geometry, trabecular microarchitecture, biomechanical strength, and sclerostin expression...

Heart failure (HF) patients with deteriorating right ventricular (RV) structure and function have a nearly two-fold increased risk of death compared to those without. Despite the well-established clinical risk, few studies have examined the molecular signature associated with this HF condition. The purpose of this study was to integrate morphologic...

Introduction Cardiovascular disease risk augments with advance of age. The mechanism of the increased cardiovascular disease risk by aging is related to attenuation of arterial function via endothelium-derived relaxing factor, such as nitric oxide (NO). Recently, apelin and adropin have identified as NO-upregulated hormones, whereas augmented secre...

The small heat shock protein 20 (HSPB6) emerges as a potential upstream mediator of autophagy. Although autophagy is linked to several clinical disorders, how HSPB6 and autophagy are regulated in the setting of heart failure (HF) remains unknown. The goal of this study was to assess activation of the HSPB6 and its association with other well-establ...

Insulin resistance in the vasculature is a characteristic feature of obesity and contributes to the pathogenesis of vascular dysfunction and disease. However, the molecular mechanisms underlying obesity-associated vascular insulin resistance and dysfunction remain poorly understood. We hypothesized that TRAF3IP2 (TRAF3 interacting protein 2), a pro...

Acute resistance exercise-induced hypertensive stimulus impairs endothelial function in males. Because prior work indicates that female subjects have a tempered blood pressure response to acute resistance exercise, we hypothesized that, compared to males, females would better maintain endothelial function following resistance exercise and that this...

We aimed to examine if individuals with type 2 diabetes (T2D) exhibit suppressed leg vascular conductance and skeletal muscle capillary perfusion in response to a hyperinsulinemic-euglycemic clamp, and to test whether these two variables are positively correlated. Subsequently, we examined if T2D-associated skeletal muscle microvascular insulin res...

Increased arterial stiffness and vascular remodeling precede and are consequences of hypertension. They also contribute to the development and progression of life-threatening cardiovascular diseases. Yet, there are currently no agents specifically aimed at preventing or treating arterial stiffening and remodeling. Previous research indicates that v...

Vasodilatory effects of insulin support the delivery of insulin and glucose to skeletal muscle. Concurrently, insulin exerts central effects that increase sympathetic nervous system activity (SNA), which is required for the acute maintenance of blood pressure (BP). Indeed, in a cohort of young healthy adults, herein we show that intravenous infusio...

Estrogen receptor-α knockout (ERKO) in female rodents results in bone loss associated with increased osteocyte sclerostin expression; whether this also occurs in males is unknown. Here, we examined the effects of ERKO on femoral cortical geometry, trabecular microarchitecture, and osteocyte sclerostin expression of the femur and lumbar vertebrae. A...

Despite efforts to reduce the incidence of type 2 diabetes (T2D) and its cardiovascular consequences, T2D‐associated cardiovascular mortality continues to rise in the US and worldwide. The presence of a pro‐inflammatory state and microvascular insulin resistance are hallmarks of T2D that contribute to cardiovascular disease. The former is associate...

Obesity and type 2 diabetes (T2D) are leading independent risk factors for cardiovascular disease morbidity and mortality. However, the precise molecular mechanisms underlying the development of cardiometabolic dysfunction in obesity and T2D remain largely elusive. The recently identified cytoplasmic adapter molecule TRAF3 Interacting Protein 2 (TR...

Beyond its metabolic actions, insulin stimulates peripheral vasodilation, which serves to increase glucose delivery to skeletal muscle. Insulin activates two distinct signaling pathways leading to the production of nitric oxide versus endothelin‐1 (ET‐1). Several lines of research suggest that insulin‐stimulated ET‐1 production may limit insulin‐st...

Vascular insulin resistance is a hallmark of type 2 diabetes (T2D) and blunting of insulin‐induced dilation is its primary manifestation. Importantly, in T2D, reduced insulin‐induced dilation and blood flow to skeletal muscle significantly limits glucose uptake and contributes to impaired glucose control. However, the mechanisms underlying vascular...

Evidence indicates sympathetic neurotransmitters influence cerebral vasomotor tone in a branch order‐dependent manner. Further, in addition to eliciting vasoconstriction, sympathetic co‐transmitter neuropeptide Y (NPY) may also elicit dilation in the cererbrovasculature depending on whether it acts on vascular smooth muscle or the endothelium. Here...

Background A Westernized lifestyle is characterized by sedentary behavior and consumption of diets high in refined sugars. This lifestyle is associated with weight gain, insulin resistance and the development of cardiovascular disease (CVD). Endothelial dysfunction is one of the key events in the pathogenesis of CVD. We have previously demonstrated...

Background Moderate intensity continuous exercise (MICT) has been shown to reduce muscle sympathetic nerve activity (MSNA) in heart failure patients with reduced ejection fraction (HFrEF). However, the effects of high‐intensity interval training (HIIT) on MSNA in HFrEF patients are unknown. We hypothesized that reductions in MSNA would be greater f...

As the prevalence of obesity continues to grow worldwide, the health and financial burden of obesity-related comorbidities grows too. Cardiovascular disease (CVD) is clearly associated with increased adiposity. Importantly, women are at higher risk of CVD when obese and insulin resistant, in particular at higher risk of developing heart failure wit...

Loss of ovarian hormones leads to increased adiposity and insulin resistance (IR), increasing the risk for cardiovascular and metabolic diseases. The purpose of this study was to investigate whether the molecular mechanism behind the adverse systemic and adipose tissue-specific metabolic effects of ovariectomy requires loss of signaling through est...

Aging causes arterial stiffening which can be mitigated by increased physical activity. Although low circulating levels of salusin-α are associated with cardiovascular disease, whether salusin-α decreases with aging and whether the reduced arterial stiffening occurring with exercise training is associated with increased serum salusin-α is unknown....

Prolonged sitting impairs leg endothelial function and this impairment is thought to be mediated by a sustained reduction in blood flow-induced shear stress. However, whether nutritional strategies can be used to prevent sitting-induced leg endothelial dysfunction remains unknown. Herein, we tested the hypothesis that 8 weeks of eicosapentaenoic ac...

Obesity and insulin resistance stiffen the vasculature with females appearing to be more adversely affected. As augmented arterial stiffness is an independent predictor of cardiovascular disease (CVD), the increased predisposition of obese and insulin-resistant women to arterial stiffening may explain their heightened risk for CVD. However, the cel...

Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide considered to be causally implicated in hypertension and the development of cardiovascular disease. Increased ET-1 is commonly associated with reduced NO bioavailability and impaired vascular function; however, whether chronic elevation of ET-1 directly impairs endothelium-dependent relaxati...

Obesity and insulin resistance stiffen the vasculature with females appearing to be more adversely affected. As augmented arterial stiffness is an independent predictor of cardiovascular disease (CVD), the increased predisposition of obese and insulin-resistant women to arterial stiffening may explain their heightened risk for CVD. However, the cel...

Insulin modulates vasomotor tone through vasodilator and vasoconstrictor signaling pathways. The purpose of the present work was to determine whether insulin-stimulated vasoconstriction is a pathophysiological phenomenon that can result from a combination of persistent insulin signaling, suppressed PI3K activation and an ensuing relative increase i...

Endothelin-1 (ET-1) is a potent vasoconstrictor and proinflammatory peptide that is upregulated in obesity. Herein, we tested the hypothesis that ET-1 signaling promotes visceral adipose tissue (AT) inflammation and disrupts glucose homeostasis. We also tested if reduced ET-1 is a required mechanism by which exercise ameliorates AT inflammation and...

The development of new treatments for heart failure lack animal models that encompass the increasingly heterogeneous disease profile of this patient population. This report provides evidence supporting the hypothesis that Western Diet−fed, aortic-banded Ossabaw swine display an integrated physiological, morphological, and genetic phenotype evocativ...

Background Prolonged sitting is associated with glycemic excursions, which are likely more pronounced within individuals with risk factors for cardiovascular disease or type 2 diabetes. Strategies to minimize inactivity during sitting are needed to offset its consequences. While chair‐based fidgeting can increase energy expenditure above basal rest...

Approximately 50% of heart failure cases are diagnosed as heart failure with preserved ejection fraction (HFpEF). HFpEF is challenging to accurately diagnose given traditional biomarkers, such as natriuretic peptide levels, have shown reduced prognostic value for HFpEF patients. Thus, the purpose of this study was to identify biomarkers considered...

Essential hypertension is a chronic idiopathic medical condition that is characterized by elevated arterial blood pressure and is associated with increased risk of cardiovascular disease. Endothelial dysfunction is associated with increased age and a casual factor for the development of hypertension. Therefore, we hypothesized that endothelial dysf...