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

American Journal of Physiology-Heart and Circulatory Physiology, Volume 321, Issue 4, Page H665-H666, October 2021.

American Journal of Physiology-Heart and Circulatory Physiology, Volume 321, Issue 4, Page H663-H664, October 2021.

Signal-averaged sympathetic transduction of blood pressure (BP) is inversely related to resting MSNA burst frequency in healthy cohorts. Whether this represents a physiological compensatory adaptation or a methodological limitation, remains unclear. The current analysis aimed to determine the contribution of methodological limitations by evaluating the dependency of MSNA transduction at different levels

Yorkshire swine were fed standard diet (n=7) or standard diet containing caffeic acid with L. plantarum (n=7) for three weeks. Next, an ameroid constrictor was placed around the left coronary circumflex artery, and the dietary regimens were continued. At fourteen weeks, cardiac function, myocardial perfusion, vascular density, and molecular signaling in ischemic myocardium were evaluated.The L. plantarum-caffeic

OBJECTIVE: Inflammation caused by infiltrating macrophages and T cells promotes plaque growth in atherosclerosis. Cadherin-11 (CDH11) is a cell-cell adhesion protein implicated in several fibrotic and inflammatory diseases. Much of the research on CDH11 concerns its role in fibroblasts, although its expression in immune cells has been noted as well. The objective of this study was to assess the effect

Alzheimer's disease (AD) has long been considered a brain-specific dementia syndrome. However, in recent decades the occurrence of cardiovascular (CV) disease in the progression of AD has been confirmed by increasing epidemiological evidence. In this study, we conducted an in-depth cardiovascular characterization of a humanized APP overexpressing mouse model (hAPP23+/-), which overexpresses the Swedish

Vascular aging is highly associated with cardiovascular morbidity and mortality. Although the senescence of vascular smooth muscle cells (VSMCs) has been well-established as a major contributor to vascular aging, intracellular and exosomal micro-RNA (miRNA) signaling pathways in senescent VSMCs have not been fully elucidated. This study aimed to identify the differential expression of intracellular

Molecular mechanisms underlying cardiac dysfunction and subsequent heart failure in diabetic cardiomyopathy are incompletely understood. Initially we intended to test the role of GRK2, a potential mediator of cardiac dysfunction in diabetic cardiomyopathy, but found that control animals on HFD did not develop cardiomyopathy. Cardiac function was preserved in both wildtype and GRK2 knockout animals

Hypertension is characterized by systemic microvascular endothelial dysfunction, in part due to a functional absence of hydrogen sulfide (H2S)-mediated endothelium-dependent dilation. Treatment with a sulfhydryl-donating ACE-inhibitor (SH-ACE-inhibitor) improves endothelial function in pre-clinical models of hypertension. To date, no studies have directly assessed the effects of SH-ACE-inhibitor treatment

Small heat shock proteins (sHsps) protect the heart from chemotherapeutics-induced heart failure, by inhibiting p53-dependant apoptosis. However, mechanism of such protection has not been elucidated yet. Here we test a hypothesis that serine phosphorylation of sHsps is essential to inhibit the Doxorubicin-induced p53-dependent apoptotic pathway. Three transgenic mice (TG) lines with cardiomyocyte specific

Aim: The role of the Na+/K+-ATPase (NKA) in heart failure associated with myocardial infarction (MI) is poorly understood. The elucidation of its precise function is hampered by the existence of two catalytic NKA isoforms (NKA-α1 and NKA-α2). Our aim was to analyze the effects of an increased NKA-α2 expression on functional deterioration and remodeling during long term MI treatment in mice and its

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

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

Background Myocardial function and exercise reserve are important determinants of outcome in pulmonary arterial hypertension (PAH) but are incompletely understood. For this study, we performed subject-specific computer simulations, based on invasive measurements and cardiac magnetic resonance imaging (CMR), to investigate whole-circulation properties in PAH at rest and exercise and determinants of

Haemoconcentration can influence hypoxic pulmonary vasoconstriction (HPV) via increased frictional force and vasoactive signalling from erythrocytes, but whether the balance of these mechanism is modified by the duration of hypoxia remains to be determined. We performed three sequential studies: (i) at sea level, in normoxia and isocapnic hypoxia with and without isovolumic haemodilution (n=10, aged

Background: Spinal cord injury (SCI) impairs the cardiovascular responses to postural challenge, leading to the development of orthostatic hypotension (OH). Here, we apply lower body negative pressure (LBNP) to rodents with high-level SCI to demonstrate the usefulness of LBNP as a model for experimental OH studies and to explore the effect of simulated OH on cardiovascular and cerebrovascular function

While pulmonary arterial hypertension (PAH) leads to right ventricle (RV) hypertrophy and structural remodeling, the relative contributions of changes in myocardial geometric and mechanical properties to systolic and diastolic chamber dysfunction and their time courses remain unknown. Using measurements of RV hemodynamic and morphological changes over 10 weeks in a male rat model of PAH and a mathematical

Airborne particulate matter (PM) is associated with an increased risk for cardiovascular diseases. When incomplete combustion of waste and fuels occurs, organics chemisorb to transition metals to generate PM-containing environmentally persistent free radicals (EPFRs). EPFRs have been detected in PM found in diesel and gasoline exhaust, woodsmoke, and urban air. Prior in vivo studies demonstrated that

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

Sphingosine-1-phosphate (S1P) is a bioactive mediator in inflammation. Dysregulated S1P is demonstrated as a cause of heart failure (HF). However, the time-dependent and integrative role of S1P interaction with receptors in HF is unclear after myocardial infarction (MI). In this study, the sphingolipid mediators were quantified in ischemic human hearts. We also measured the time-kinetics of these mediators

Acute damage to the heart, as in the case of myocardial infarction (MI), triggers a robust inflammatory response to the sterile injury that is part of a complex and highly organized wound healing process. Cortical bone stem cell (CBSC) therapy after MI has been shown to reduce adverse structural and functional remodeling of the heart after MI in both mouse and swine models. The basis for these CBSC

β-Adrenergic receptors (βAR) regulate normal and pathophysiological heart function through their impact on contractility. βAR are also regulators of immune function where they play a unique role depending on the disease condition and immune cell type. Emerging evidence suggests an important role for the β2AR subtype in regulating remodeling in the pathological heart, however, the importance of these

Cardiac dysfunction in heart failure (HF) and diabetic cardiomyopathy (DCM) is associated with aberrant intracellular Ca2+ handling and impaired mitochondrial function accompanied with reduced mito-[Ca2+]. Pharmacological or genetic facilitation of mito-Ca2+ uptake was shown to restore Ca2+ transient amplitude in DCM and HF, improving contractility. However, recent reports suggest that pharmacological

The endothelin‐B (ETB) receptor is a key regulator of vascular endothelial function in women. We have previously shown that the ETB receptor mediates vasodilation in young women, an effect that is lost after menopause. However, the direct impact of changes in estradiol (E2) on ETB receptor function in women remains unclear. Therefore, the purpose of this study was to test the hypothesis that E2 exposure

Ventricular arrhythmias, consisting of single ectopic beats (sEB), multiple EB (mEB), and Torsades de Pointes (TdP, defined as >5 beats with QRS vector twisting around isoelectric line) can be induced in the anesthetized chronic AV-block (CAVB) dog by dofetilide (IKr-blocker). The interplay between temporal dispersion of repolarization, quantified as short-term variability (STV), and spatial dispersion

Tumor necrosis factor alpha (TNFa) in the hypothalamic paraventricular nucleus (PVN) contributes to increased sympathetic nerve activity (SNA) in cardiovascular disease models, but mechanisms are incompletely understood. As previously reported, bilateral PVN TNFa (0.6 pmol, 50 nL) induced acute ramping of splanchnic SNA (SSNA) that averaged +64 ± 7% after 60 min and +109 ± 17% after 120 min (P<0.0001

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

Chronic insufficient sleep is a common occurrence around the world, and results in numerous physiological detriments and consequences, including cardiovascular complications. The purpose of the present study was to assess the relationship between habitual total sleep time (TST) measured objectively via at-home actigraphy and heart rate (HR) reactivity to nocturnal cortical arousals. We hypothesized

Adverse childhood experiences (ACEs) are psychosocial stressors that occur during sensitive developmental windows and are associated with increased lifetime cardiovascular disease (CVD) risk in a dose-dependent manner. Vascular endothelial dysfunction is a pathophysiological mechanism that promotes hypertension and CVD, and may be a mechanism by which ACEs contribute to lifetime CVD risk. We examined

The anterior cerebral artery (ACA) supplies blood predominantly to the frontal lobe including the prefrontal cortex. Our laboratory reported that prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) increases prior to and at exercise onset, as long as exercise is arbitrarily started. Moreover, the increased prefrontal oxygenation seems independent of both exercise intensity and muscle mass. If so

Recent findings suggest that COVID-19 causes vascular dysfunction during the acute phase of the illness in otherwise healthy young adults. To date, no studies have investigated the longer-term effects of COVID-19 on vascular function. Herein, we hypothesized that young, otherwise healthy adults who are past the acute phase of COVID-19 would exhibit blunted peripheral (brachial artery flow-mediated

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

Previous studies suggest that parental obesity may adversely impact long-term metabolic health of the offspring. We tested the hypothesis that parental (paternal + maternal) obesity impairs cardiac function in the offspring early in life. Within 1-3 days after weaning, offspring from obese rats fed a high fat diet (HFD-Offs) and age-matched offspring from lean rats (ND-Offs) were submitted to echocardiography

Pulmonary arterial hypertension (PAH) is a fatal cardiopulmonary disease characterized by increased vascular cell proliferation with resistance to apoptosis and occlusive remodeling of the small pulmonary arteries in humans. The Notch family of proteins are proximal signaling mediators of an evolutionarily conserved pathway that effect cell proliferation, fate determination, and development. In endothelial

Angiotensin II (Ang II) plays an important role in the regulation of various physiological functions including proliferation, hypertrophy of vascular smooth muscle cells (VSMC) through the overexpression of Giα proteins. Sirtuin1 (Sirt1), a class III histone deacetylase and epigenetic regulator is implicated in a wide range of cellular functions, including migration and growth of VSMC as well as in

An exaggerated exercise pressor reflex (EPR) causes excessive sympatho-excitation and exercise intolerance during physical activity in the chronic heart failure (CHF) state. Muscle afferent sensitization contributes to the genesis of the exaggerated EPR in CHF. However, the cellular mechanisms underlying muscle afferent sensitization in CHF remain unclear. Considering that voltage-gated potassium (Kv)

In conditions with abnormally increased activity of the cardiac ryanodine receptor (RyR2), Ca2+/calmodulin-dependent protein kinase II (CaMKII) can contribute to a further destabilization of RyR2 that results in triggered arrhythmias. Therefore, inhibition of CaMKII in such conditions has been suggested as a strategy to suppress RyR2 activity and arrhythmias. However, suppression of RyR2 activity can

Background: Left ventricular (LV) remodeling, characterized by increased LV hypertrophy and depressed function, is observed in strength-trained athletes who use anabolic-androgenic steroids (AAS). Previous studies reported an increase in cardiac fibrosis in these athletes, which could promote intraventricular dyssynchrony. In this context, this study evaluated LV dyssynchrony in strength-trained athletes

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 vital to identify newer targets and strategies to reduce

American Journal of Physiology-Heart and Circulatory Physiology, Volume 321, Issue 1, Page H254-H255, July 2021.

American Journal of Physiology-Heart and Circulatory Physiology, Volume 321, Issue 1, Page H253-H253, July 2021.

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

In a progressively aging population, it is of utmost importance to develop reliable, noninvasive, and cost-effective tools to estimate biomarkers which can be indicative of cardiovascular risk. Various pathophysiological conditions are associated to changes in the total arterial compliance (CT), and thus its estimation via an accurate and simple method is valuable.Direct noninvasive measurement of

Introduction: Detailed global maps of atrial electrical activity are needed to understand mechanisms of atrial rhythm disturbance in small animal models of heart disease. To date, optical mapping systems have not provided enough spatial resolution across sufficiently extensive regions of intact atrial preparations to achieve this goal. Objectives: To develop an integrated platform for quantifying regional

Background: Cardiopulmonary sympathetic control is exerted via stellate ganglia, however, little is known about how neuronal firing patterns in the stellate ganglion relate to dynamic physiologic function in the heart and lungs. Methods: We performed continuous extracellular recordings from SG neurons using multielectrode arrays in chloralose-anesthetized pigs (n=6) for 8-9 hours. Respiratory and left

Voxelotor (also known as GBT440) is a hemoglobin S polymerization inhibitor that increases the hemoglobin (Hb) affinity for oxygen (O2) in blood and has been approved for the treatment of sickle cell disease (SCD). In this study, GBT1118, an analog of voxelotor, was used to assess the impact of increasing Hb affinity for O2 on brain tissue oxygenation, blood pressure, heart rate, O2 delivery, and tolerance

Background. Deep-learning (DL) has been applied for automatic left ventricle (LV) ejection fraction (EF) measurement, but the diagnostic performance was rarely evaluated for various phenotypes of heart disease. This study aims to evaluate a new DL algorithm for automated LVEF measurement using two-dimensional echocardiography (2DE) images collected from 3 centers. The impact of 3 ultrasound machines

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

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

Electronic cigarettes (E-cigs) have been promoted as harm-free or less-risky than smoking, even for women during pregnancy. These claims are made largely on E-cig aerosol having fewer number of toxic chemicals compared to cigarette smoke. Given that even low levels of smoking are found to produce adverse birth outcomes, we sought to test the hypothesis that vaping during pregnancy (with or without

Pulmonary hypertension (PH) observed during respiratory syncytial virus (RSV) bronchiolitis is associated with morbidity and mortality, especially in children with congenital heart disease. Yet, the pathophysiological mechanisms of RSV-associated PH remain unclear. Therefore, this study aimed to investigate the pathophysiological mechanism of RSV-associated PH. We employed a translational mouse model

American Journal of Physiology-Heart and Circulatory Physiology, Volume 321, Issue 1, Page H161-H161, July 2021.

Dual-specificity phosphatases (DUSPs) serve critical roles in the regulation of mitogen-activated protein kinases, but their functions in the cardiovascular system remain poorly defined. Here, we provide evidence that DUSP5, which resides in the nucleus and specifically dephosphorylates extracellular signal-regulated kinase (ERK1/2), blocks pulmonary vascular smooth muscle cell proliferation. In response

Arterial stiffness, a consequence of smoking, is an underlying risk factor of cardiovascular diseases. Epoxyeicosatrienoic acids (EETs), hydrolyzed by soluble epoxide hydrolase (sEH), have beneficial effects against vascular dysfunction. However, the role of sEH knockout in nicotine-induced arterial stiffness was not characterized. We hypothesized that sEH knockout could prevent nicotine-induced arterial

Ethanol consumption represents a significant public health problem, and excessive ethanol intake is a risk factor for cardiovascular disease (CVD), one of the leading causes of death and disability worldwide. The mechanisms underlying the effects of ethanol on the cardiovascular system are complex and not fully comprehended. The gut microbiota and their metabolites are indispensable symbionts essential

Sympathetic activation is an established trigger of life-threatening cardiac events in long QT syndrome type 1 (LQT1). KCNQ1 loss-of-function variants, which underlie LQT1, have been associated with both cardiac arrhythmia and neuronal hyperactivity pathologies. However, the LQT1 sympathetic neuronal phenotype is unknown. Here we aimed to study human induced pluripotent stem cell (hiPSC)-derived sympathetic

Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by recurrent or unresolved pulmonary thromboemboli, leading to perfusion defects and increased arterial wave reflections. CTEPH treatment aims to reduce pulmonary arterial pressure and reestablish adequate lung perfusion, yet patients with distal lesions are inoperable by standard surgical intervention. Instead, these patients undergo

The etiology of ethanol-related congenital heart defects has been the focus of much study, but most research has concentrated on cellular and molecular mechanisms. We have shown with optical coherence tomography (OCT) that ethanol exposure led to increased retrograde flow and smaller atrioventricular (AV) cushions compared to controls. Since AV cushions play a role in patterning the conduction delay

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