Aging causes deleterious changes in resting conduit artery shear patterns and reduced blood flow during exercise partially attributable to reduced nitric oxide (NO). Inorganic nitrate increases circulating NO bioavailability and may therefore improve age-associated changes in shear rate as well as exercise hyperemia. 10 older adults (67±3yrs) consumed 4.03mmol nitrate and 0.29mmol nitrite (active)

Aging is associated with increased risk of cardiovascular and cerebrovascular events, which are preceded by early, negative remodeling of the vasculature. Low physical activity is a well-established risk factor associated with the incidence and development of disease. However, recent physical activity literature indicates the importance of considering the 24-hour movement spectrum. Therefore, the purpose

The pathological involvement of anion channels in vascular dysfunction that occurs during type 2 diabetes (T2D) is unclear. Here, we tested the hypothesis that TMEM16A, a calcium (Ca2+)-activated chloride (Cl-) channel, contributes to modifications in arterial contractility during T2D. Our data indicate that T2D increased TMEM16A mRNA in arterial smooth muscle cells (myocytes) and total and surface

Pannexin1 (Panx1) channels export ATP and may contribute to increased concentration of the vasodilator ATP in plasma during hypoxia in vivo. We hypothesized that Panx1 channels and associated ATP export contributes to hypoxic vasodilation, a mechanism that facilitates the matching of oxygen delivery to tissue metabolic demand. Male and female mice devoid of Panx1 (Panx1-/-) and wild-type controls (WT)

Introduction: Transient Receptor Potential Vanilloid 4 (TRPV4) channel is a calcium permeable channel (PCa/PNa ~ 10). Its expression was reported in ventricular myocytes where it is involved in several cardiac pathological mechanisms. In this study, we investigated the implication of TRPV4 in ventricular electrical activity. Methods and Results: Left ventricular myocytes were isolated from trpv4+/+and

Comprehensive functional characterization of cardiac tissue includes investigation of length and load dependence. Such measurements have been slow to develop in engineered heart tissues (EHTs), whose mechanical characterizations have been limited primarily to isometric and near-isometric behaviors. A more realistic assessment of myocardial function would include force-velocity curves to characterize

Background: CaMKIId is needed for the recovery of Ca2+ transients during acidosis, but also mediates post-acidic arrhythmias. CaMKIId can sustain its activity following oxidation. Increasing intracellular Na+ during acidosis as well as post-acidic pH normalization should result in pro-oxidant conditions within the cell favoring oxidative CaMKIId activation. Rationale: We tested whether oxidative CaMKIId

American Journal of Physiology-Heart and Circulatory Physiology, Volume 320, Issue 1, Page H469-H470, January 2021.

American Journal of Physiology-Heart and Circulatory Physiology, Volume 320, Issue 1, Page H471-H473, January 2021.

Since their origin over one half-century ago, microneurographic recordings of sympathetic nerve activity have significantly advanced our understanding of the generation and regulation of central sympathetic outflow in human health and disease. For example, it is now appreciated that a myriad of disease states exhibit chronic sympathetic overactivity, a significant predictor of cardiovascular morbidity

Increased regurgitant blood flow has been linked to endocardial cushion defects and resultant congenital heart diseases (CHDs). Prenatal alcohol exposure (PAE) has been shown to alter early blood flow resulting in abnormal endocardial cushions and CHDs. Compounds, including folic acid (FA), mitigate PAE effects and prevent CHDs, but few studies have assessed their effects on blood flow. We modeled

Although sodium-glucose co-transporter 1 (SGLT1) has been identified as one of the major SGLT isoforms expressed in the heart, its exact role remains elusive. Evidences using phlorizin, the most common inhibitor of SGLTs, suggested its role in glucose transport. However, phlorizin could also affect classical facilitated diffusion via glucose transporters (GLUTs), bringing into question the relevance

Background: Residential proximity to greenness is associated with a lower risk of cardiovascular disease (CVD) and all-cause mortality. However, it is unclear whether the beneficial effects of greenness are linked to a reduction in the effects of ambient air pollutants. Methods and Results: We measured arterial stiffness in 73 participants with moderate to high CVD risk. Average levels of ambient PM2

Insufficient sleep is associated with endothelial vasomotor dysfunction and increased cardiovascular risk. Regular aerobic exercise is an effective lifestyle strategy for improving endothelial function and, in turn, reducing cardiovascular risk. We tested the hypotheses that regular aerobic exercise would: 1) improve endothelial vasodilation; and 2) decrease ET-1-mediated vasoconstrictor tone in middle-aged

Acute exhaustive endurance exercise can differentially impact the right ventricle (RV) versus the left (LV). However, the hemodynamic basis for these differences and its impact on post-exercise recovery remains unclear. Therefore, we assessed cardiac structure and function along with hemodynamic properties of mice subjected to single bouts (216±8min) of exhaustive swimming (ES). One-hour after ES,

Angiotensin II (AngII) is a key mediator of the renin-angiotensin system and plays an important role in the regulation of cardiac electrophysiology by affecting various cardiac ion currents, including transient outward potassium current Ito. AngII receptors and molecular components of Ito, Kv4.2 and Kv4.3 channels, have been linked to caveolae structures. However, their functional interaction as well

Perinatal hypoxia induces permanent structural and functional changes in the lung and its pulmonary circulation that are associated with the development of pulmonary hypertension (PH) in later life. The mechanistic target of the rapamycin (mTOR) pathway is vital for fetal lung development and implicated in hypoxia-associated PH, yet its involvement in the developmental programming of PH remains unclear

We aimed to determine: 1) the mechanism(s) that enable glucose-6-phosphate dehydrogenase (G6PD) to regulate serum response factor (SRF)- and myocardin (MYOCD)‑driven smooth muscle cell (SMC)-restricted gene expression, a process that aids in the differentiation of SMCs; and 2) whether G6PD-mediated metabolic reprogramming contributes to the pathogenesis of vascular diseases in metabolic syndrome (MetS)

Exosomes are an important mechanism of cell-cell interaction in the cardiovascular system, both in maintaining homeostasis and in stress response. Interindividual differences that alter content in exosomes may play a role in cardiovascular disease pathology. To study the effect of interindividual cardiomyocyte (CM) variation, we characterized exosomal content in phenotypically diverse human induced

Viral myocarditis (VMC) is a life-threatening disease characterized by severe cardiac inflammation generally caused by coxsackievirus B3 (CVB3) infection. Several microRNAs (miRNAs or miRs) are known to play crucial roles in the pathogenesis of VMC. The study aims to decipher the role of miR-30a-5p in the underlying mechanisms of VMC pathogenesis. We first quantified miR-30a-5p expression in a CVB3-induced

The use of physiological models in medicine allows the evaluation of new hypotheses, development of diagnosis and clinical treatment applications, development of training and medical education tools, as well as medical device design. Although several mathematical models of physiological systems have been presented in the literature, few of them are able to predict the human cardiorespiratory response

Atherosclerosis is a dynamic process starting with endothelial dysfunction and inflammation and eventually leading to life-threatening arterial plaques. Exercise generally improves endothelial function in a dose-dependent manner by altering hemodynamics, specifically by increased arterial pressure, pulsatility, and shear stress. However, athletes who regularly participate in high-intensity training

Spiral wave reentry as a mechanism of lethal ventricular arrhythmias has been widely demonstrated in animal experiments and recordings from human hearts. It has been shown that in structurally normal hearts, spiral waves are unstable, breaking up into multiple wavelets via dynamical instabilities. However, many of the second-generation action potential models give rise only to stable spiral waves,

People with intellectual disability (ID) experience cardiometabolic related morbidity and mortality. However, it has been suggested that this population present and live with underestimated cardiovascular risk factors at a younger age, hence affecting their overall health, quality of life and contributing to early mortality. We assessed autonomic nervous system function in subjects with ID (n=39),

Chirality is a fundamental property in many biologic systems. Motivated by previous observations of helical aortic blood flow, aortic tissue fibers, and propagation of aortic dissections, we introduce methods to characterize helical morphology of aortic dissections. After validation on computer generated phantoms, the methods were applied to patients with type B dissection. For this cohort, there was

Vascular cells restructure extracellular matrix in response to aging or changes in mechanical loading. Here, we characterized collagen architecture during age-related aortic remodeling in atherosclerosis-prone mice. We hypothesized that changes in collagen fiber orientation reflect an altered balance between passive and active forces acting on the arterial wall. We examined two factors that can alter

In spite of advances in the diagnosis and treatment of ischemic heart disease (IHD), it remains the leading cause of death globally. Thus, there is an urgent demand to investigate the underlying pathophysiology and develop new therapies for the prevention and treatment of IHD. Murine models are widely used in IHD research because they are readily available, relatively inexpensive and can be genetically

Mechanical dyssynchrony (MD) affects left ventricular (LV) mechanics and coronary perfusion. To understand the multifactorial effects of MD, we developed a computational model that bi-directionally couples the systemic circulation with the LV and coronary perfusion with flow regulation. In the model, coronary flow in the left anterior descending (LAD) and left circumflex (LCX) arteries affects the

With each heartbeat, the right ventricle (RV) inputs blood into the pulmonary vascular (PV) compartment which conducts blood through the lungs at low pressure and concurrently fills the left atrium (LA) for output to the systemic circulation. This overall hemodynamic function of the integrated RV-PV-LA unit is determined by complex interactions between the components that vary over the cardiac cycle

Dysfunction of late endothelial progenitor cells (EPCs) has been suggested to be associated with hypertension. β2 adrenergic receptor (β2AR) is a novel and key target for EPCs homing. Here, we proposed that attenuated β2AR signaling contributes to EPCs dysfunction, whereas enhanced β2AR signaling restores EPCs' functions in hypertension. EPCs derived from hypertensive patients exhibited reduced cell

Butyrate is a short-chain fatty acid (SCFA) derived from microbiota and is involved in a range of cell processes in a concentration-dependent manner. Low concentrations of sodium butyrate (NaBu) was shown to be proangiogenic. However, the mechanisms associated with these effects are not yet fully known. Here, we investigated the contribution of the SCFA receptor GPR43 in the proangiogenic effects of

Most studies on ischemic preconditioning (IPC) use one or two ischemic stimuli, before examining cardioprotection. In order to better simulate the clinical situation, we examined, in pigs, the effects of 6 episodes of 10 min coronary artery occlusion (CAO) 12 hours apart, followed by 60 min CAO. We named this model the 4th window of IPC. In order to determine the novel mechanisms mediating cardioprotection

Previous studies showed that conduit artery blood flow rapidly increases after even a brief contraction of muscles within the dependent limb. Whether this rapid hyperemia occurs within contracted skeletal muscle in humans has yet to be confirmed, however. We therefore used diffuse correlation spectroscopy (DCS) to characterize the rapid hyperemia and vasodilatory responses within the muscle microvasculature

Over two thirds of individuals aged 65 and older are obese or overweight in the United States. Epidemiological data show an association between the degree of adiposity and cognitive dysfunction in the elderly. In this review, the pathophysiological roles of microvascular mechanisms, including impaired endothelial function and neurovascular coupling responses, microvascular rarefaction and blood-brain

The complex pathophysiology of atrial fibrillation (AF) is governed by multiple risk factors in ways that are still elusive. Basic electrophysiological properties including atrial effective refractory period (AERP) and conduction velocity are major factors determining the susceptibility of the atrial myocardium to AF. Although there is a great need for affordable animal models in this field of research

The prevalence of cardiovascular diseases dramatically increases with age, therefore striving to maintain a physiological heart function became particularly important. We aimed to study the voluntary exercise evoked cardioprotective effects in aged male and female rats, from genetic alterations to changes in heart performance. We divided 20-month-old female and male Wistar rats to control and running

Peripherally or centrally administered TNF-α elicits a prolonged sympathetically mediated pressor response, but the underlying molecular mechanisms are unknown. Activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in cardiovascular regions of the brain has recently been recognized as a key mediator of sympathetic excitation, and ERK1/2 signaling is induced by activation of epidermal

The integrin family, an indispensable part of cell-cell and cell-matrix interactions, consists of a group of heterodimeric adhesion receptors formed by α and β integrin subunits. Their wide expression and unique bi-directional signaling pathways allow them to play roles in a variety of biological activities including blood clot formation, cell attachment, and migration. Evidence suggests that integrins

Background Magnetic resonance imaging (MRI) of the right ventricle (RV) offers important diagnostic information, but the accuracy of this information is hampered by the complex geometry of the RV. In this project, we propose a novel post-processing algorithm that corrects for partial-volume effects in the analysis of standard MRI cine images of RV mass (RVm), and evaluate the method in clinical and

Morbidity and mortality associated with heart disease is a growing threat to the global population and novel therapies are needed. Mavacamten (formerly called MYK-461) is a small molecule that binds to cardiac myosin and inhibits myosin ATPase. Mavacamten is currently in clinical trials for the treatment of obstructive hypertrophic cardiomyopathy (HCM), and it may provide benefits for treating other

Creatine kinase (CK) is considered the main phosphotransfer system in the heart, important for overcoming diffusion restrictions and regulating mitochondrial respiration. It is substrate limited in creatine-deficient mice lacking L-arginine:glycine amidinotransferase (AGAT) or guanidinoacetate methyltranferase (GAMT). Our aim was to determine the expression, activity and mitochondrial coupling of hexokinase

Background: While SARS-CoV-2 primarily affects the lungs, the virus may be inflicting detriments to the cardiovascular system, both directly through angiotensin converting enzyme 2 receptor as well as initiating systemic inflammation. Persistent systemic inflammation may be provoking vascular dysfunction, an early indication of cardiovascular disease risk. Methods: In order to establish the potential

This study aimed to elucidate the effects of change in estrogen during the menstrual cycle and menopause on shear-mediated dilation of the internal carotid artery (ICA), a potential index of cerebrovascular endothelial function. Shear-mediated dilation of the ICA and serum estradiol were measured in 11 premenopausal (Pre-M, 21±1yrs), 13 perimenopausal (Peri-M, 49±2yrs), and 10 postmenopausal (Post-M

Passive leg movement (PLM) evokes a robust and predominantly nitric oxide (NO)-mediated increase in blood flow that declines with age and disease. Consequently, PLM is becoming increasingly accepted as a sensitive assessment of endothelium-mediated vascular function. However, a substantial PLM-induced hyperemic response is still evoked despite NO synthase (NOS) inhibition. Therefore, in 9 young healthy

Diabetes mellitus (DM) is one of the primary pathological factors that contributes to aging-related cognitive impairments, but the underlying mechanisms remain unclear. We recently reported that old DM rats exhibited impaired myogenic responses of the cerebral arteries and arterioles, poor cerebral blood flow autoregulation, enhanced blood-brain barrier (BBB) leakage, and cognitive impairments. These

Heart failure (HF) is one of the leading causes of mortality and morbidity in the modern world whose increasing prevalence is associated with "Western" diet and sedentary lifestyles. Of particular concern is the increasing burden of HF with preserved ejection fraction (HFpEF) that involves complex pathophysiology and is difficult to treat. Pressure overload caused by hypertension (HTN) is the predominant

Brain capillary pericytes have been suggested to play a role in the regulation of cerebral blood-flow under physiological and pathophysiological conditions. ATP has been shown to cause constriction of capillaries under ischemic conditions and suggested to be involved in the "no-reflow" phenomenon. In order to investigate the effects of extracellular ATP on pericyte cell contraction, we studied purinergic

In human heart failure and in murine hearts with left ventricular pressure overload (LVPO), increases in fibrosis are associated with increases in stiffness. Secreted Protein Acidic and Rich in Cysteine (SPARC) is necessary for both cardiac fibrosis and increases in myocardial stiffness in response to LVPO, however cellular sources of cardiac SPARC are incompletely defined. Irradiation and bone marrow

Exercise-related mitral regurgitation (Ex-MR) is one of the mechanisms that contribute to reduced functional capacity in heart failure (HF). Its prevalence is not well defined across different HF subtypes. The aim of the present study is to describe functional phenotypes and cardiac response to exercise in HFrEF, HFmrEF and HFpEF, according with Ex-MR prevalence. A total of 218 HF patients (146 men

Atrial fibrillation (AF), the most common persistent arrhythmia, is terminated most effectively by electrical cardioversion. This therapy requires in-hospital sedation to relieve the pain caused by the electric shocks. Recently, our research group showed how the heart itself could be enabled to detect and terminate arrhythmias, including AF, thereby revealing the discovery of fully biological, shock-free

Vascular epithelial Na+ channels (ENaCs) made up of canonical α, β, and γ subunits have attracted more attention recently due to their physiological role in vascular health and disease. A fourth subunit δ-ENaC is expressed in various mammalian species, except mice and rats, which are common animal models for cardiovascular research. Accordingly, δ-ENaC is the least understood subunit. However, the

Biological sex is increasingly recognized as a critical determinant of health and disease, particularly relevant to the topical COVID-19 pandemic caused by the SARS-CoV-2 coronavirus. Epidemiological data and observational reports from both the original SARS epidemic and the most recent COVID-19 pandemic have a common feature: males are more likely to exhibit enhanced disease severity and mortality

The use of spontaneous bursts of muscle sympathetic nerve activity (MSNA) to assess arterial baroreflex control of sympathetic nerve activity has seen increased utility in studies of both health and disease. However, methods used for analyzing spontaneous MSNA baroreflex sensitivity are highly variable across published studies. Therefore, we sought to comprehensively examine methods of producing linear

In sleep apnea, airway obstruction causes intermittent hypoxia (IH). In animal studies, IH-dependent hypertension is associated with loss of vasodilator hydrogen sulfide (H2S), and increased H2S activation of sympathetic nervous system (SNS) activity in the carotid body. We previously reported that inhibiting cystathionine γ-lyase (CSE) to prevent H2S synthesis augments vascular resistance in control

Alpha-1-Adrenergic receptors (ARs) are catecholamine-activated G protein-coupled receptors (GPCRs) that are expressed in mouse and human myocardium and vasculature and play essential roles in the regulation of cardiovascular physiology. Though alpha-1-ARs are less abundant in the heart than beta-1-ARs, activation of cardiac alpha-1 ARs results in important biologic processes such as hypertrophy, positive

Our prior work has shown that Na+current (INa) affects sarcoplasmic reticular (SR) Ca2+release by activating early reverse of the Na+-Ca2+exchanger (NCX). The resulting Ca2+ entry primes the dyadic cleft, which appears to increase Ca2+channel coupling fidelity. It has been shown that the skeletalisoform of the voltage-gated Na+channel (Nav1.4) is the main tetrodotoxin(TTX)-sensitive Navisoform expressed

It is generally accepted that older adults display an impaired cardiovascular response to heat stress, and it has been suggested that this impaired response contributes to their increased risk of mortality during extreme heat events. Seminal studies have shown that cutaneous vasodilation, the redistribution of blood flow from visceral organs and the increase in cardiac output are blunted in older adults

Pathological cardiac remodeling is a leading cause of mortality in diabetic patients. Given the glucose and lipid metabolism disorders (GLD) in diabetic patients, it is urgent to conduct a comprehensive study of the myocardial damage under GLD and find key mechanisms. Apolipoprotein E knockout (ApoE-/-) mice, low-density lipoprotein receptor heterozygote (Ldlr+/-) syrian golden hamsters or H9C2 cells