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-established autophagy markers in central and peripheral tissues

Atrial fibrillation (AF) is the most common cardiac arrhythmia characterised by irregular atrial activity. AF is related to increased risk of thromboembolic events, heart failure, and premature mortality. Recent advances in our understanding of its pathophysiology include a potentially central role for inflammation and presence of cardiovascular risk factors. The role of physical activity and exercise

Mixed venous oxygen (O2) saturation (SvO2) is an important measure to evaluate sufficiency of cardiac output (CO) relative to whole body O2 consumption (VO2), while clinical utilization is limited for required invasive catheterization. By Fick's equation, VO2 (ml/min) = CO (L/min) x Hb (g/dL) x 1.36 (ml/g) x (SaO2 - SvO2) / 10 [Hb = hemoglobin concentration, SaO2 = arterial blood O2 saturation]. Since

The arcuate nucleus of hypothalamus (ARC) plays a key role in linking peripheral metabolic status to the brain melanocortin system, which influences a wide range of physiological processes including the sympathetic nervous system and blood pressure. The importance of the activity of agouti-related peptide (AgRP)- and proopiomelanocortin (POMC)-expressing neurons, two molecularly distinct populations

Chronic inflammatory disorders, including rheumatoid arthritis (RA), are associated with a two-fold increase in the incidence of sudden cardiac death (SCD) compared to the healthy population. Although this is partly explained by an increased prevalence of coronary artery disease, growing evidence suggests that ischaemia alone cannot completely account for the increased risk. The present review explores

Cardiopulmonary arrest (CA) is the leading cause of death and disability in the United States. CA-induced brain injury is influenced by multi-factorial processes, including reduced cerebral blood flow (hypoperfusion) and neuroinflammation, which can lead to neuronal cell death and functional deficits. We have identified serum and glucocorticoid-regulated kinase-1 (SGK1) as a new target in brain ischemia

Objective: Oscillometry is an alternative to continuous wave-Doppler (cw-Doppler) to determine peripheral artery disease (PAD) severity using the ankle-brachial-index (ABI). Cw-Doppler-ABI differentiates systolic pressure of ATP and ADP where either one of both values in most patients is higher (high) and the other value is lower (low). In contrast, oscillometric-ABI measures the strongest signal and

Background: Pulmonary arterial hypertension (PAH) is a refractory disease. Its prognosis remains poor; hence, establishment of novel therapeutic targets is urgent. TP53-induced glycolysis and apoptosis regulator (TIGAR) is a downstream target of p53, and exhibits functions inhibiting autophagy and reactive oxygen species (ROS). Recently, p53 was shown to suppress the PAH progression. Since inhibition

Transient receptor potential proteins (TRPs) act as non-selective cation channels. Of the TRP channels, PC2- also known as polycystin 2- is localized to the sarcoplasmic reticulum (SR), however its contribution to calcium induced calcium release (CICR) and overall cardiac function in the heart is poorly understood. The goal of this study was to characterize the effect of cardiac specific PC2 deletion

Coordinating blood flow to active tissue requires vasomotor responses to conduct among resistance arteries. Vasomotor spread is governed by the electrical and mechanical properties of vessels; the latter being linked to the sigmoid relations between membrane potential (VM), [Ca2+], and smooth muscle contractility. Proteins guiding electrical-to-tone translation are subject to regulation; thus, vasomotor

Elevated sympathetic vasomotor tone seen in heart failure (HF) may involve dysfunction of the hypothalamic paraventricular nucleus neurons that project to the rostral ventrolateral medulla (PVN‒RVLM neurons). This study aimed to elucidate the role of PVN‒RVLM neurons in the maintenance of resting renal sympathetic nerve activity (RSNA) after myocardial infarction (MI). In male rats, the left coronary

High altitude exposure typically reduces endothelial function, and this is modulated by hemoconcentration resulting from plasma volume contraction. However, the specific impact of hypobaric hypoxia, independent of external factors (e.g. cold, varying altitudes, exercise, diet, dehydration) on endothelial function is unknown. We examined the temporal changes in blood viscosity, shear stress and endothelial

The 60 kDa heat shock protein (HSP60) is a chaperone essential for mitochondrial proteostasis ensuring thus sufficient aerobic energy production. In pathological conditions, HSP60 can be translocated from the mitochondria and excreted from the cell. In turn, the extracellular HSP60 has a strong ability to trigger and enhance inflammatory response with marked pro-inflammatory cytokine induction, which

Heat acclimation (HA) may improve the regulation of cardiac output (Q̇) through increased blood volume (BV) and left ventricular (LV) diastolic filling, and attenuate reductions in Q̇ during exercise-induced dehydration; however, these hypotheses have never been directly tested. Before and following 10-days exercise HA, eight males completed two trials of submaximal exercise in 33°C and 50% relative

Heart rate variability (HRV) is a measure of variation in time interval between heartbeats and reflects the influence of autonomic nervous system and circulating/locally released factors on sinoatrial node discharge. Here, we tested whether electrocardiograms (ECGs) obtained in conscious, restrained mice, a condition that affects sympathovagal balance, reveal alterations of heart rhythm dynamics with

In patients with myocardial infarction (MI), cardiac rupture is an uncommon, but catastrophic complication. In the mouse model of non-reperfused MI, reported rupture rates are highly variable, and depend not only on the genetic background and sex of animals, but also on the method used for documentation of rupture. In most studies, diagnosis of cardiac rupture is based on visual inspection during autopsy;

In patients with heart failure, atrial septal defect (ASD) closure has a risk to induce life-threatening acute pulmonary edema. The objective of this study was to develope a novel framework for quantitative prediction of hemodynamics after ASD closure. The generalized circulatory equilibrium comprises right and left cardiac output (CO) curves, and pulmonary and systemic venous return surfaces. We incorporated

Nitric oxide (NO)-mediated endothelial dysfunction, secondary to increased oxidative stress, presents in young African American (AA) compared to European American (EA) adults, and may be modulated by vitamin D status. We assessed cutaneous microvascular function in 18 young, healthy (21±2 yr; 9 M, 9 F) subjects before (pre: 8 AA, 10 EA) and 13 subjects after (post: 7 AA, 6 EA) four weeks of 2,000 IU/day

Fluctuations in diastolic pressure modulates muscle sympathetic nerve activity (MSNA) through the arterial baroreflex. A higher sympathetic baroreflex sensitivity (sBRS) to pressure falls compared to rises has been reported, however, the underlying mechanisms are unclear. We assessed whether beat-to-beat falling and rising diastolic pressures operate on two distinct baroreflex response curves. Twenty-two

In univentricular (Fontan) physiology, peripheral and splanchnic vascular tone may be raised to counteract reduced cardiac output (CO) and elevated central venous pressure, and thus maintain vital organ perfusion. This could negatively affect the normal cardiovascular response to food ingestion, where mesenteric vasodilation and a concurrent rise in CO are central. We sought to elucidate this using

It was classically thought that the function of mammalian red blood cells (RBC) was limited to serving as a vehicle for oxygen, given the cell's abundance of cytosolic haemoglobin. Over the past decades, however, accumulating evidence indicates that RBC have the capacity to sense low oxygen tensions in hypoxic tissues, and subsequently release signalling molecules that influence the distribution of

We have previously reported enhanced Ca2+ sensitivity of coronary arteries that are dependent upon collateral circulation for their blood supply. For the current study, we hypothesized that small collateral-dependent arteries would exhibit an enhanced KCl-mediated contractile response attributable to Ca2+ sensitization and increased Ca2+ channel current. Ameroid constrictors were surgically placed

Cardiac alternans, defined as beat-to-beat alternations in action potential duration, cytosolic Ca transient (CaT) amplitude and cardiac contraction, is associated with atrial fibrillation (AF) and sudden cardiac death. At the cellular level, cardiac alternans is linked to abnormal intracellular calcium handling during excitation-contraction coupling. We investigated how pharmacological activation

Objectives: Postconditioning attenuates inflammation and fibrosis in myocardial infarction (MI). Aim of this study was to investigate whether postconditioning with the CpG-containing TLR9-ligand 1668-thioate (CpG) can modulate inflammation and remodeling in reperfused murine MI. Methods: Thirty min. LAD-occlusion was conducted in 12 weeks old C57BL/6 mice. Mice were treated with CpG i.p. 5 min. before

Aims. Ubiquitylation is a key event that regulates protein turnover, and induction of the ubiquitin ligase E3 WWP1 has been associated with age. Left ventricular hypertrophy (LVH) commonly occurs as a function of age and can cause heart failure with a preserved ejection fraction (EF; HFpEF). We hypothesized that overexpression of WWP1 in the heart would cause LVH as well as functional and structural

Sympathetic neurons (SNs) capable of modulating the heart rate of murine cardiomyocytes (CMs) can be differentiated from human stem cells. The electrophysiological properties of human stem cell derived SNs remain largely uncharacterised, and human neurocardiac cocultures remain to be established. Here we have adapted previously published differentiation and coculture protocols to develop feeder-free

Patients with type 2 diabetes mellitus (T2DM) exhibit diminished exercise capacity likely attributable to reduced skeletal muscle blood flow (i.e., exercise hyperemia). A potential underlying mechanism of the impaired hyperemic response to exercise could be inadequate blunting of sympathetic-mediated vasoconstriction (i.e., poor functional sympatholysis). Therefore, we studied the hyperemic and vasodilatory

This study used an integrative experimental model in humans to investigate whether muscle angiogenic factors are differentially modulated by exercise stimuli eliciting different degrees of mechanical and metabolic stress. In a randomized crossover design, twelve men performed two low‑volume high-intensity exercise regimens, including short sprint intervals (SSI) or long sprint intervals (LSI) inducing

Cardiovascular disease is a major cause of morbidity and mortality worldwide. Innovative new treatment options for this cardiovascular pandemic are urgently needed. Activation of purinergic receptors (PRs) is critically involved in the development and progression of cardiovascular disease including atherosclerosis, ischemic heart disease, hypertension and diabetes. PRs have been targeted for the treatment

BACKGROUND: The efficacy of an anthracycline antibiotic doxorubicin (DOX) as a chemotherapeutic agent is limited by dose-dependent cardiotoxicity. DOX is associated with activation of intracellular stress signaling pathways including p38 MAPKs. While previous studies have implicated p38 MAPK signaling in DOX-induced cardiac injury, the roles of the individual p38 isoforms, specifically, of the alternative

A lower heart rate (HR) during heat exposure is a classic marker of heat acclimation (HA), although it remains unclear whether this adaptation occurs secondary to reduced thermal strain and/or improvements in cardiac function. We evaluated the hypothesis that short-term passive HA reduces HR and improves cardiac function during passive heating. Echocardiography was performed under thermoneutral and

Methyltransferases are a superfamily of enzymes that transfer methyl groups to proteins, nucleic acids and small molecules. Traditionally, these enzymes have been shown to carry out a specific modification (mono-, di- or trimethylation) on a single, or limited number of, amino acid(s). The largest subgroup of this family, protein methyltransferases, target arginine and lysine side chains of histone

Diastolic dysfunction (DD) is a major component of heart failure with preserved ejection fraction (HFpEF). Accordingly, a profound understanding of the underlying biomechanical mechanisms involved in DD is needed in order to elucidate all aspects of HFpEF. In this study, we have developed a computational model of DD by leveraging the power of an advanced one-dimensional (1D) arterial network coupled

Hypercholesterolemia and atherosclerosis caused vasomotor properties dysfunction may be involved in many clinic manifestations of atherosclerosis, including angina, acute myocardial infarction, and sudden cardiac death. However, its underlying mechanism is not clear. The endothelial glycocalyx is a protective surface layer on the endothelial cells, serving as a molecular sieve, cell adhesion modulator

Our objective was to investigate the effect of desmin depletion on the structure and function of the sinoatrial pacemaker complex, (SANcl) and their implication in arrhythmogenesis. Analysis of mice and human (SANcl) indicated that SAN exhibits high amounts of desmin, desmoplakin, N-cadherin and β-catenin in structures we call "lateral IDs", connecting myocytes side-by-side. Examination of the SANcl

Salt intake may alter blood pressure (BP) regulation, but no study has investigated the impact of salt reduction versus salt loading on morning blood pressure surge (MBPS) and sympathetic neural control in premenopausal women with a history of normal pregnancy. Nine healthy women [42±3 (SD) yr] were given a low-salt (LS; 50 mEq sodium/day) and high-salt diet (HS; 250 mEq sodium/day) for 1 week each

COVID-19 and Diabetes Outcomes (CORONADO) trial revealed that 10.6% of diabetes mellitus patients hospitalized for coronavirus disease 2019 (COVID-19) and die within 7 days. Several studies from New York, Italy, and China confirm that diabetic patients are at a much high risk for mortality due to COVID-19. Besides respiratory illness, COVID-19 increases cardiac injury, and diabetic ketoacidosis. In

Myeloperoxidase (MPO)-derived hypochlorous (HOCl) reacts with membrane plasmalogens to yield α-chlorofatty aldehydes such as 2-chlorofatty aldehyde (2-ClFALD) and its metabolite 2-chlorofatty acid (2-ClFA). Recent studies showed that 2-ClFALD and 2-ClFA serve as mediators of the inflammatory responses to sepsis by as yet unknown mechanisms. Since no scavenger for chlorinated lipids is available and

Duchenne muscular dystrophy (DMD) is an X-linked disease caused by null mutations in dystrophin and characterized by muscle degeneration. Cardiomyopathy is common and often prevalent at similar frequency in female DMD carriers irrespective of whether they manifest skeletal muscle disease. Impaired muscle nitric oxide (NO) production in DMD disrupts muscle blood flow regulation and exaggerates post-exercise

The right ventricle (RV) is often overlooked in the evaluation of cardiac performance and treatment of left ventricular (LV) heart diseases. However, recent evidence suggests the RV may play an important role in maintaining systemic cardiac function and delivering stroke volume (SV). We used exercise cardiac magnetic resonance and biomechanical modeling to investigate the role of the RV in LV stroke

Vascular smooth muscle cells (VSMCs) are the fundamental component of the medial layer of arteries and are essential for arterial physiology and pathology. It is becoming increasingly clear that VSMCs can alter their metabolism to fulfill the bio-energetic and biosynthetic requirements. During vascular injury, VSMCs switch from a quiescent "contractile" phenotype to a highly migratory and proliferative

Left ventricular (LV) structural remodeling following athletic training has been evidenced through training-specific changes in wall thickness and geometry. Whether the LV response to changes in hemodynamic load also adapts in a training-specific manner is unknown. Using echocardiography, we examined LV responses of endurance-trained (n=15), resistance-trained (n=14), and non-athletic males (n=13)

Preeclampsia is a major complication of pregnancy manifested as hypertension and often intrauterine growth restriction, but the underlying pathophysiological mechanisms are unclear. Predisposing genetic and environmental factors cause placental maladaptations leading to defective placentation, apoptosis of invasive cytotrophoblasts, inadequate expansive remodeling of the spiral arteries, reduced uteroplacental

American Journal of Physiology-Heart and Circulatory Physiology, Ahead of Print.

Patients presenting classical cardiovascular risk factors within acceptable or average value ranges often develop cardiovascular disease, suggesting that other risk factors need to be considered. Considering that endothelial progenitor cells (EPC) contribute to endothelial repair, we investigated whether EPC might be such a factor. We compared the ability of peripheral blood EPC to attach to extracellular

An ischemic insult is accompanied by an acute increase in circulating fatty acid (FA), which can induce adverse changes related to cardiac metabolism/energetics. Although chronic hyperlipidemia contributes to the pathogenesis of obesity/diabetes-related cardiomyopathy, it unclear how these hearts are affected by an acute high FA-load. We hypothesize that adaptation to chronic FA exposure enhances the

Since mitral valve (MV) complex (MVC) longitudinally bridges left ventricular (LV) base-end and its middle, insufficient MVC longitudinal tissue length (TL) elongation relative to whole LV myocardial longitudinal TL elongation could limit LV-base-longitudinal-TL elongation, leading to predominant LV-base-transverse-TL elongation, constituting LV spherical remodeling. In 30 patients with dilated cardiomyopathy

Analyses of individual atherosclerotic plaques are mostly descriptive, relying - for example - on histological classification by spectral analysis of ultrasound waves or staining and observing particular cellular components. Such passive methods have proved useful for characterizing the structure and vulnerability of plaques but have little quantitative predictive power. Our aim is to introduce and

Insulin-like growth factor-1 (IGF-1) decreases atherosclerosis in Apolipoprotein E (Apoe) -deficient mice when administered systemically. However, mechanisms for its atheroprotective effect are not fully understood. We generated endothelium-specific IGF-1 receptor (IGF1R) deficient mice on Apoe-deficient background to assess effects of IGF-1 on the endothelium in the context of hyperlipidemia-induced

Although increased predisposition to cardiac fibrosis and cardiac dysfunction has been demonstrated in the perinatally nicotine exposed heart, the underlying mechanisms remain unclear. Using a well-established rat model and cultured primary neonatal rat cardiac fibroblasts, the effect of perinatal nicotine exposure on offspring heart extracellular matrix deposition and the likely underlying mechanisms

Tobacco cigarette (TC) smoking has never been lower in the United States, but electronic cigarette (EC) vaping has reached epidemic proportions among our youth. Endothelial dysfunction, as measured by flow-mediated vasodilation (FMD) is a predictor of future atherosclerosis and adverse cardiovascular events and is impaired in young TC smokers, but whether FMD is also reduced in young EC vapers is uncertain

In 2017, the American Heart Association (AHA) and American College of Cardiology (ACC) redefined stage 1 hypertension to systolic blood pressure (BP) 130–139 mmHg or diastolic BP 80–89 mmHg; however, the degree to which microvascular endothelial dysfunction is evident in adults with stage 1 hypertension remains equivocal. We tested the hypotheses that cutaneous microvascular endothelial dysfunction

It has been suggested that sex differences in acute blood pressure fluctuations occur during the periods of time between bursts of muscle sympathetic nerve activity. Therefore, we tested the hypothesis that men experience more dynamic changes in mean arterial pressure (Finometer MIDI) than women during acute sympathoinhibition (i.e., slow breathing) in which bursts of sympathetic activity occur more

Cardiac electrophysiology and mechanics are strongly interconnected. Calcium is crucial in this complex interplay through its role in cellular electrophysiology and sarcomere contraction. We aim to differentiate the effects of acute β-adrenergic stimulation (β-ARS) and cardiomyocyte stretch (increased sarcomere length) on calcium-transient dynamics and force generation, using a novel computational

The lymphatic system drains and propels lymph by extrinsic and intrinsic mechanisms. Intrinsic propulsion depends upon spontaneous rhythmic contractions of lymphatic muscles in the vessel walls and is critically affected by changes in the surrounding tissue like osmolarity and temperature. Lymphatics of the diaphragm display a steep change in contraction frequency in response to changes in temperature

Peripheral artery disease (PAD) is a manifestation of atherosclerosis in the leg arteries, which causes claudication. This may be in part due to vascular mitochondrial dysfunction and excessive reactive oxygen species (ROS) production. A mitochondrial-targeted antioxidant (MitoQ) has been shown to improve vascular mitochondrial function that, in turn, led to improved vascular function in older adults

Proper inlet boundary conditions are essential for accurate computational fluid dynamics (CFD) modeling. We developed methodology to derive noninvasive FFRB using CFD and computed tomography coronary angiography (CTCA) images. This study aims to assess the influence of brachial mean blood pressure (MBP) and total coronary inflow on FFRB computation. Twenty-two patients underwent both CTCA and FFR measurements