10,541 results match your criteria American Journal Of Physiology-heart And Circulatory Physiology[Journal]


Chronic Stress and Endothelial Dysfunction: Mechanisms, Experimental Challenges and Way Ahead.

Am J Physiol Heart Circ Physiol 2020 Jul 3. Epub 2020 Jul 3.

Physiological Sciences, Stellenbosch University, South Africa.

Although chronic stress is an important risk factor for cardiovascular diseases (CVD) onset, the underlying mechanisms driving such pathophysiologic complications remain relatively unknown. Here, dysregulation of innate stress response systems and the effects of downstream mediators are strongly implicated, with the vascular endothelium emerging as a primary target of excessive glucocorticoid and catecholamine action. This review article therefore explores the development of stress-related endothelial dysfunction by focusing on the following: 1) assessing the phenomenon of stress and complexities surrounding this notion; 2) discussing mechanistic links between chronic stress and endothelial dysfunction; and 3) evaluating the utility of various preclinical models currently employed to study mechanisms underlying the onset of stress-mediated complications such as endothelial dysfunction. Read More

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http://dx.doi.org/10.1152/ajpheart.00244.2020DOI Listing

Call for papers on racial differences in cardiovascular and cerebrovascular physiology.

Am J Physiol Heart Circ Physiol 2020 Jul 3. Epub 2020 Jul 3.

Department of Cellular and Integrative Physiology, University of Nebraska, United States.

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http://dx.doi.org/10.1152/ajpheart.00524.2020DOI Listing

Image-based scaling laws for somatic growth and pulmonary artery morphometry from infant- to adulthood.

Am J Physiol Heart Circ Physiol 2020 Jul 3. Epub 2020 Jul 3.

Pediatrics Cardiology, Stanford University, United States.

Pulmonary artery (PA) morphometry has been extensively explored in adults, with particular focus on intra-acinar arteries. However, scaling law relationships for length and diameter of extensive pre-acinar PAs by age have not been previously reported for in vivo human data. To understand pre-acinar PA growth spanning children to adults, we performed morphometric analyses of all PAs visible in the computed tomography (CT) and magnetic resonance (MR) images from a healthy subject cohort (n=16; age: 1-51 years; body surface area, BSA: 0. Read More

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http://dx.doi.org/10.1152/ajpheart.00123.2020DOI Listing

Dilated Cardiomyopathy Mutations in Thin Filament Regulatory Proteins Reduce Contractility, Suppress Systolic Ca & Activate NFAT & AKT Signalling.

Am J Physiol Heart Circ Physiol 2020 Jul 3. Epub 2020 Jul 3.

Radcliffe Department of Medicine (Division of Cardiovascular Medicine), University of Oxford, United Kingdom.

Dilated cardiomyopathy (DCM) is clinically characterised by dilated ventricular cavities and reduced ejection fraction, leading to heart failure and increased thromboembolic risk. Mutations in thin filament regulatory proteins can cause DCM and have been shown in vitro to reduce contractility and myofilament Ca-affinity. In this work we have studied the functional consequences of mutations in cardiac troponin T (R131W), cardiac troponin I (K36Q) and α-tropomyosin (E40K) using adenovirally transduced isolated guinea pig left ventricular cardiomyocytes. Read More

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http://dx.doi.org/10.1152/ajpheart.00272.2020DOI Listing

Progesterone promotes endothelial nitric oxide synthase expression through enhancing nuclear progesterone receptor-SP1 formation.

Am J Physiol Heart Circ Physiol 2020 Jul 3. Epub 2020 Jul 3.

Cardiology, The First Affiliated Hospital of Chongqing Medical University, China.

Progesterone exerts antihypertensive actions partially by modulating endothelial nitric oxide synthase (eNOS) activity. Here, we aimed to investigate the effects and mechanisms of progesterone on eNOS expression. Firstly,HUVECs (human umbilical vein endothelial cells) were exposed to progesterone, then the eNOS、transcription factor SP1 (Specificity protein 1) and PR-A/B (progesterone receptor) expression were assessed by Western blotting and qRT-PCR. Read More

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http://dx.doi.org/10.1152/ajpheart.00206.2020DOI Listing

The Role of Endothelial Autocrine NRG1/ERBB4 Signaling in Cardiac Remodeling.

Am J Physiol Heart Circ Physiol 2020 Jul 3. Epub 2020 Jul 3.

Laboratory of Physiopharmacology, University of Antwerp, Belgium.

Neuregulin-1 (NRG1) is a paracrine growth factor, secreted by cardiac endothelial cells (ECs) in conditions of cardiac overload/injury. The current concept is that the cardiac effects of NRG1 are mediated by activation of ERBB4/ERBB2 receptors on cardiomyocytes. However, recent studies have shown that paracrine effects of NRG1 on fibroblasts and macrophages are equally important. Read More

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http://dx.doi.org/10.1152/ajpheart.00176.2020DOI Listing

Pressure-Overload Generates a Cardiac-Specific Profile of Inflammatory Mediators.

Am J Physiol Heart Circ Physiol 2020 Jun 26. Epub 2020 Jun 26.

Medicine-Cardiology, Medical University of South Carolina, United States.

Mechanisms that contribute to myocardial fibrosis, particularly in response to left ventricular pressure-overload (LVPO), remain poorly defined. To test the hypothesis that a myocardial-specific profile of secreted factors is produced in response to PO, levels of 44 factors implicated in immune cell recruitment and function were assessed in a murine model of cardiac hypertrophy and compared to levels produced in a model of pulmonary fibrosis (PF). Mice subjected to PO were assessed at one and four weeks. Read More

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http://dx.doi.org/10.1152/ajpheart.00274.2020DOI Listing

Development of an endothelial cell restricted transgenic reporter rat: A resource for physiological studies of vascular biology.

Am J Physiol Heart Circ Physiol 2020 06 26. Epub 2020 Jun 26.

Physiology and Cell Biology, University of South Alabama, United States.

Here, we report the generation of a Cre-recombinase transgenic rat, where iCre is driven using a CDH5 promoter. The CDH5 promoter was cloned from rat pulmonary microvascular endothelial cells and demonstrated approximately 60% similarity to the murine counterpart. The cloned rat promoter was 2,508 bp, it extended 79 bp beyond the transcription start site, and it was 22,923 bp upstream of the translation start site. Read More

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http://dx.doi.org/10.1152/ajpheart.00276.2020DOI Listing

LncRNA-SMILR modulates RhoA/ROCK signaling by targeting miR-141 to regulate vascular remodeling in pulmonary arterial hypertension.

Am J Physiol Heart Circ Physiol 2020 Jun 19. Epub 2020 Jun 19.

Department of Respiratory Medicine, the Second Xiangya Hospital of Central South University, China.

Background: Pulmonary arterial hypertension (PAH) is a fatal progressive disease characterized by an increased blood pressure in the pulmonary arteries. RhoA/Rho-kinase (RhoA/ROCK) signaling activation is often associated with PAH. The purpose of this study is to investigate the role and mechanisms of long non-coding RNA (lncRNA) Smooth muscle-induced lncRNA (SMILR) to activate RhoA/ROCK pathway in PAH. Read More

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http://dx.doi.org/10.1152/ajpheart.00717.2019DOI Listing

Sensory nerve-mediated and nitric oxide-dependent cutaneous vasodilation in normotensive and prehypertensive non-Hispanic Blacks and Whites.

Am J Physiol Heart Circ Physiol 2020 Jun 19. Epub 2020 Jun 19.

Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, United States.

The purpose of this study was to investigate the effect of race and subclinical elevations in blood pressure (i.e., prehypertension) on cutaneous sensory nerve-mediated and NO-dependent vasodilation. Read More

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http://dx.doi.org/10.1152/ajpheart.00177.2020DOI Listing

Cardiovascular Adaptations to Particle Inhalation Exposure: Molecular Mechanisms of the Toxicology.

Am J Physiol Heart Circ Physiol 2020 Jun 19. Epub 2020 Jun 19.

Exercise Physiology, West Virginia University School of Medicine, United States.

Ambient air, occupational settings, and the use and distribution of consumer products all serve as conduits for toxicant exposure through inhalation. While the pulmonary system remains a primary target following inhalation exposure, cardiovascular implications are exceptionally culpable for increased morbidity and mortality. The epidemiological evidence for cardiovascular dysfunction resulting from acute or chronic inhalation exposure to particulate matter has been well documented, but the mechanisms driving the resulting disturbances remain elusive. Read More

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http://dx.doi.org/10.1152/ajpheart.00026.2020DOI Listing

Altered endothelial ET receptor expression in postmenopausal women.

Am J Physiol Heart Circ Physiol 2020 Jul 19;319(1):H242-H247. Epub 2020 Jun 19.

Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware.

The endothelin system plays an important role in mediating vascular function. The endothelin-B receptor (ETR) on endothelial cells mediates vasodilation via nitric oxide production. The vasodilatory effect of the ETR is lost following menopause and may contribute to impaired vascular endothelial function in postmenopausal women (PMW). Read More

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http://dx.doi.org/10.1152/ajpheart.00342.2020DOI Listing

The hERG channel activator, RPR260243, enhances protective I current in early refractory reducing arrhythmogenicity in zebrafish hearts.

Am J Physiol Heart Circ Physiol 2020 Jun 19. Epub 2020 Jun 19.

Biomedical Physiology and Kinesiology, Simon Fraser University, Canada.

hERG K channels are important in cardiac repolarization and their dysfunction causes prolongation of the ventricular action potential, Long QT Syndrome, and arrhythmia. As such, approaches to augment hERG channel function, such as activator compounds, have been of significant interest due to their marked therapeutic potential. Activator compounds that hinder channel inactivation abbreviate action potential duration (APD), but carry risk of over-correction leading to Short QT Syndrome. Read More

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http://dx.doi.org/10.1152/ajpheart.00038.2020DOI Listing

Acute and Chronic Sympathomimetic Effects of E-Cigarette and Tobacco Cigarette Smoking: Role of Nicotine and Non-Nicotine Constituents.

Am J Physiol Heart Circ Physiol 2020 Jun 19. Epub 2020 Jun 19.

Medicine, UCLA, United States.

Electronic cigarettes(ECs) and tobacco cigarettes(TCs) both release nicotine, a sympathomimetic drug. We hypothesized that baseline heart rate variability(HRV) and hemodynamics would be similar in chronic EC and TC-smokers, and that after acute EC use, changes in HRV and hemodynamics would be attributable to nicotine, not non-nicotine constituents in EC aerosol. In 100 smokers, including 58 chronic EC-users and 42 TC-smokers, baseline HRV and hemodynamics (blood pressure[BP] and heart rate[HR]) were compared. Read More

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http://dx.doi.org/10.1152/ajpheart.00192.2020DOI Listing

The role of transient receptor potential channels in cerebral myogenic autoregulation in hypertension and aging.

Am J Physiol Heart Circ Physiol 2020 Jul 19;319(1):H159-H161. Epub 2020 Jun 19.

Department of Neurosurgery, Medical School, University of Pecs, Hungary.

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http://dx.doi.org/10.1152/ajpheart.00403.2020DOI Listing

Mechanisms of increased vascular stiffness down the aortic tree in aging, premenopausal female monkeys.

Am J Physiol Heart Circ Physiol 2020 Jul 12;319(1):H222-H234. Epub 2020 Jun 12.

Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers, New Jersey Medical School, Newark, New Jersey.

Protection against increased vascular stiffness in young women is lost after menopause. However, little is known about vascular stiffness in older, premenopausal females, because most of the prior work has been conducted in rodents, which live for only 1-3 yr and do not go through menopause. The goal of the current investigation was to quantitate differences in stiffness down the aortic tree and the mechanisms mediating those differences in older, premenopausal (24 ± 0. Read More

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http://dx.doi.org/10.1152/ajpheart.00153.2020DOI Listing

Thromboxane A Receptors Mediate Chronic Mechanoreflex Sensitization in a Rat Model of Simulated Peripheral Artery Disease.

Am J Physiol Heart Circ Physiol 2020 Jun 12. Epub 2020 Jun 12.

Kinesiology, Kansas State University, United States.

The exercise pressor reflex is a feedback autonomic and cardiovascular control mechanism evoked by mechanical and metabolic signals within contracting skeletal muscles. The mechanically sensitive component of the reflex (the mechanoreflex) is exaggerated in peripheral artery disease (PAD) patients and in a rat model of simulated PAD in which a femoral artery is chronically ligated. Products of cyclooxygenase enzyme activity have been shown to chronically sensitize the mechanoreflex in PAD but the identity of the muscle afferent receptors that mediate the sensitization is unclear. Read More

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http://dx.doi.org/10.1152/ajpheart.00255.2020DOI Listing

Is Teamwork Still Possible during a Global Pandemic?

Authors:
Irving H Zucker

Am J Physiol Heart Circ Physiol 2020 Jul 5;319(1):H1-H2. Epub 2020 Jun 5.

Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska.

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http://dx.doi.org/10.1152/ajpheart.00408.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303720PMC

ASIC1a does not play a role in evoking the metabolic component of the exercise pressor reflex in a rat model of peripheral artery disease.

Am J Physiol Heart Circ Physiol 2020 Jul 5;319(1):H171-H182. Epub 2020 Jun 5.

Heart and Vascular Institute, Pennsylvania State College of Medicine, Hershey, Pennsylvania.

The role of the ASIC1a in evoking the exercise pressor reflex in rats with simulated peripheral artery disease is unknown. This prompted us to determine whether ASIC1a plays a role in evoking the exaggerated exercise pressor reflex in decerebrated rats with simulated peripheral artery disease. To simulate peripheral artery disease, we ligated the left femoral artery 72 h before the experiment. Read More

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http://dx.doi.org/10.1152/ajpheart.00257.2020DOI Listing

Tead1 is essential for mitochondrial function in cardiomyocytes.

Am J Physiol Heart Circ Physiol 2020 Jul 5;319(1):H89-H99. Epub 2020 Jun 5.

Division of Cardiology, Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania.

Mitochondrial dysfunction occurs in most forms of heart failure. We have previously reported that Tead1, the transcriptional effector of Hippo pathway, is critical for maintaining adult cardiomyocyte function, and its deletion in adult heart results in lethal acute dilated cardiomyopathy. Growing lines of evidence indicate that Hippo pathway plays a role in regulating mitochondrial function, although its role in cardiomyocytes is unknown. Read More

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http://dx.doi.org/10.1152/ajpheart.00732.2019DOI Listing
July 2020
3.838 Impact Factor

Mechanisms of sympathetic restraint in human skeletal muscle during exercise: role of α-adrenergic and nonadrenergic mechanisms.

Am J Physiol Heart Circ Physiol 2020 Jul 5;319(1):H192-H202. Epub 2020 Jun 5.

Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Dallas, Dallas, Texas.

Sympathetic vasoconstriction is mediated by α-adrenergic receptors under resting conditions. During exercise, increased sympathetic nerve activity (SNA) is directed to inactive and active skeletal muscle; however, it is unclear what mechanism(s) are responsible for vasoconstriction during large muscle mass exercise in humans. The aim of this study was to determine the contribution of α-adrenergic receptors to sympathetic restraint of inactive skeletal muscle and active skeletal muscle during cycle exercise in healthy humans. Read More

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http://dx.doi.org/10.1152/ajpheart.00208.2020DOI Listing

AMPK activation in pregnant human myometrial arteries from high-altitude and intrauterine growth-restricted pregnancies.

Am J Physiol Heart Circ Physiol 2020 Jul 5;319(1):H203-H212. Epub 2020 Jun 5.

Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado.

High-altitude (>2,500 m) residence increases the incidence of intrauterine growth restriction (IUGR) due, in part, to reduced uterine artery blood flow and impaired myometrial artery (MA) vasodilator response. A role for the AMP-activated protein kinase (AMPK) pathway in protecting against hypoxia-associated IUGR is suggested by genomic and transcriptomic studies in humans and functional studies in mice. AMPK is a hypoxia-sensitive metabolic sensor with vasodilatory properties. Read More

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http://dx.doi.org/10.1152/ajpheart.00644.2019DOI Listing

Sympathetically mediated increases in cardiac output, not restraint of peripheral vasodilation, contribute to blood pressure maintenance during hyperinsulinemia.

Am J Physiol Heart Circ Physiol 2020 Jul 5;319(1):H162-H170. Epub 2020 Jun 5.

Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri.

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 infusion of insulin increases muscle SNA while BP is maintained. Read More

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http://dx.doi.org/10.1152/ajpheart.00250.2020DOI Listing

Within-breath sympathetic baroreflex sensitivity is modulated by lung volume but unaffected by acute intermittent hypercapnic hypoxia in men.

Am J Physiol Heart Circ Physiol 2020 Jul 5;319(1):H213-H221. Epub 2020 Jun 5.

Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Sciences, University of British Columbia, Kelowna, British Columbia, Canada.

Muscle sympathetic nerve activity (MSNA) exhibits well-described within-breath respiratory modulation, but the interactive contributions of the arterial baroreflex remain unclear. The present study assessed ) within-breath modulation of sympathetic baroreflex sensitivity (BRS) and ) the effect of acute intermittent hypercapnic hypoxia (IHH) on within-breath sympathetic BRS and respiratory-sympathetic entrainment. Seventeen men (24 ± 4 yr) underwent an 8- to 10-min spontaneously breathing baseline while continuous measures of blood pressure (BP), heart rate, MSNA, ventilation, and end-tidal gases were collected. Read More

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http://dx.doi.org/10.1152/ajpheart.00296.2020DOI Listing

Cooling-induced dilatation of cutaneous arteries is mediated by increased myoendothelial communication.

Am J Physiol Heart Circ Physiol 2020 Jul 29;319(1):H123-H132. Epub 2020 May 29.

Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland.

Cold exposure causes cutaneous vasoconstriction via a reflex increase in sympathetic activity and a local effect to augment adrenergic constriction. Local cooling also initiates cutaneous dilatation, which may function to restrain cold-induced constriction. However, the underlying mechanisms and physiological role of cold-induced dilatation have not been defined. Read More

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http://dx.doi.org/10.1152/ajpheart.00159.2020DOI Listing

The novel P2X7 receptor antagonist PKT100 improves cardiac function and survival in pulmonary hypertension by direct targeting of the right ventricle.

Am J Physiol Heart Circ Physiol 2020 Jul 29;319(1):H183-H191. Epub 2020 May 29.

Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.

In pulmonary hypertension (PH) a proinflammatory milieu drives pulmonary vascular remodeling, maladaptive right ventricular (RV) remodeling, and right-sided heart failure. There is an unmet need for RV-targeted pharmaco-therapies to improve mortality. Targeting of the P2X7 receptor (P2X7R) reduces pulmonary pressures; however, its effects on the RV are presently unknown. Read More

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http://dx.doi.org/10.1152/ajpheart.00580.2019DOI Listing

Doxorubicin contributes to thrombus formation and vascular injury by interfering with platelet function.

Am J Physiol Heart Circ Physiol 2020 Jul 29;319(1):H133-H143. Epub 2020 May 29.

Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.

In clinical studies, platelet aggregation and risk of thrombosis are increased in patients after doxorubicin treatment. However, the exact role of doxorubicin in platelet functions and thrombus formation in vivo remain unclear. The present study is to investigate the role of doxorubicin in platelet function in relation to thrombus formation and vascular toxicity, as well as the efficacy of antiplatelet therapy. Read More

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http://dx.doi.org/10.1152/ajpheart.00456.2019DOI Listing

Optimal cutting temperature medium embedding and cryostat sectioning are valid for cardiac myofilament function assessment.

Am J Physiol Heart Circ Physiol 2020 Jul 29;319(1):H235-H241. Epub 2020 May 29.

Department of Medical Cell Biology, Integrative Physiology, Uppsala University, Uppsala Sweden.

To maximize data obtainment from valuable cardiac tissue, we hypothesized that myocardium fixed in optimal cutting temperature (OCT) medium for histology could also be used to investigate the function of myofilament proteins in situ. We compared tissue prepared via conventional liquid nitrogen (LN) snap freezing with tissue fixed in OCT and then sectioned in fiber-parallel orientation. We found that actin-myosin Ca sensitivity, activation rate by Ca, cooperativity along the thin filament, as well as cross-bridge cycling rate were unaffected by OCT storage and could reliably be interpreted after sectioning. Read More

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http://dx.doi.org/10.1152/ajpheart.00194.2020DOI Listing
July 2020
3.838 Impact Factor

Conduit arterial wave reflection promotes pressure transmission but impedes hydraulic energy transmission to the microvasculature.

Am J Physiol Heart Circ Physiol 2020 Jul 22;319(1):H66-H75. Epub 2020 May 22.

Heart Research, Murdoch Children's Research Institute, Parkville, Victoria, Australia.

Current thinking suggests that wave reflection in arteries limits pulse pressure and hydraulic energy (HE) transmission to the microvasculature and that this protective effect reduces with advancing age. However, according to transmission line theory, pressure transmission (T) and reflection (R) coefficients are proportional (T = 1 + R), implying that wave reflection would promote rather than limit pressure transmission. We hypothesized that increasing distal pulse pressure (PPd) with age is instead related to increased proximal pulse pressure (PPp) and its forward component and that these are modulated by arterial compliance. Read More

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http://dx.doi.org/10.1152/ajpheart.00733.2019DOI Listing

Neurovascular coupling is not influenced by lower body negative pressure in humans.

Am J Physiol Heart Circ Physiol 2020 Jul 22;319(1):H22-H31. Epub 2020 May 22.

Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

Cerebral blood flow is tightly coupled with local neuronal activation and metabolism, i.e., neurovascular coupling (NVC). Read More

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http://dx.doi.org/10.1152/ajpheart.00076.2020DOI Listing
July 2020
3.838 Impact Factor

The effects of exercise training on lipid metabolism and coronary heart disease.

Am J Physiol Heart Circ Physiol 2020 Jul 22;319(1):H76-H88. Epub 2020 May 22.

Dipartimento di Scienze e Tecnologie Biologiche e Ambientali, Università del Salento, Lecce, Italy.

Blood lipoproteins are formed by various amounts of cholesterol (C), triglycerides (TGs), phospholipids, and apolipoproteins (Apos). ApoA1 is the major structural protein of high-density lipoprotein (HDL), accounting for ~70% of HDL protein, and mediates many of the antiatherogenic functions of HDL. Conversely, ApoB is the predominant low-density lipoprotein (LDL) Apo and is an indicator of circulating LDL, associated with higher coronary heart disease (CHD) risk. Read More

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http://dx.doi.org/10.1152/ajpheart.00708.2019DOI Listing

Cardiac mesenchymal cells from failing and nonfailing hearts limit ventricular dilation when administered late after infarction.

Am J Physiol Heart Circ Physiol 2020 Jul 22;319(1):H109-H122. Epub 2020 May 22.

Diabetes and Obesity Center, Department of Medicine, University of Louisville, Louisville, Kentucky.

Although cell therapy-mediated cardiac repair offers promise for treatment/management of heart failure, lack of fundamental understanding of how cell therapy works limits its translational potential. In particular, whether reparative cells from failing hearts differ from cells derived from nonfailing hearts remains unexplored. Here, we assessed differences between cardiac mesenchymal cells (CMC) derived from failing (HF) versus nonfailing (Sham) hearts and whether the source of donor cells (i. Read More

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http://dx.doi.org/10.1152/ajpheart.00114.2020DOI Listing

Redistribution of cardiac output during exercise by functional mitral regurgitation in heart failure: compensatory O peripheral uptake to delivery failure.

Am J Physiol Heart Circ Physiol 2020 Jul 22;319(1):H100-H108. Epub 2020 May 22.

Cardiology University Department, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Donato, University of Milano, Milano, Italy.

Functional mitral regurgitation (MR) is prognostic in heart failure (HF). MR favors an nonphysiological exercise central cardiac output (CO) redistribution which adds to oxygen (O) delivery failure. The consequences of this redistribution in O supply have not been explored previously. Read More

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http://dx.doi.org/10.1152/ajpheart.00125.2020DOI Listing

Glucose-6-phosphate dehydrogenase increases Ca currents by interacting with Ca1.2 and reducing intrinsic inactivation of the L-type calcium channel.

Am J Physiol Heart Circ Physiol 2020 Jul 22;319(1):H144-H158. Epub 2020 May 22.

Department of Pharmacology, New York Medical College, Valhalla, New York.

Pyridine nucleotides, such as NADPH and NADH, are emerging as critical players in the regulation of heart and vascular function. Glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway, is the primary source and regulator of cellular NADPH. In the current study, we have identified two isoforms of G6PD (slow and fast migrating) and functionally characterized the slow migrating isoform of G6PD (G6PD) in bovine and human arteries. Read More

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http://dx.doi.org/10.1152/ajpheart.00727.2019DOI Listing

Coordinated regulation of cell survival and cell cycle pathways by DDR2-dependent SRF transcription factor in cardiac fibroblasts.

Am J Physiol Heart Circ Physiol 2020 06 15;318(6):H1538-H1558. Epub 2020 May 15.

Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India.

Relative resistance to apoptosis and the ability to proliferate and produce a collagen-rich scar determine the critical role of cardiac fibroblasts in wound healing and tissue remodeling following myocardial injury. Identification of cardiac fibroblast-specific factors and mechanisms underlying these aspects of cardiac fibroblast function is therefore of considerable scientific and clinical interest. In the present study, gene knockdown and overexpression approaches and promoter binding assays showed that discoidin domain receptor 2 (DDR2), a mesenchymal cell-specific collagen receptor tyrosine kinase localized predominantly in fibroblasts in the heart, acts via ERK1/2 MAPK-activated serum response factor (SRF) transcription factor to enhance the expression of antiapoptotic cIAP2 in cardiac fibroblasts, conferring resistance against oxidative injury. Read More

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http://dx.doi.org/10.1152/ajpheart.00740.2019DOI Listing

Chronic cigarette smoke exposure triggers a vicious cycle of leukocyte and endothelial-mediated oxidant stress that results in vascular dysfunction.

Am J Physiol Heart Circ Physiol 2020 Jul 15;319(1):H51-H65. Epub 2020 May 15.

Division of Cardiovascular Medicine, Department of Internal Medicine, Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio.

Although there is a strong association between cigarette smoking exposure (CSE) and vascular endothelial dysfunction (VED), the underlying mechanisms by which CSE triggers VED remain unclear. Therefore, studies were performed to define these mechanisms using a chronic mouse model of cigarette smoking (CS)-induced cardiovascular disease mirroring that in humans. C57BL/6 male mice were subjected to CSE for up to 48 wk. Read More

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http://dx.doi.org/10.1152/ajpheart.00657.2019DOI Listing

attenuates cardiac injury without lowering cholesterol in low-density lipoprotein receptor-deficient mice fed standard chow.

Am J Physiol Heart Circ Physiol 2020 Jul 15;319(1):H32-H41. Epub 2020 May 15.

Department of Nutritional Sciences, University of Arizona, Tucson, Arizona.

Disruption of the normal gut microbiome (dysbiosis) is implicated in the progression and severity of myriad disorders, including hypercholesterolemia and cardiovascular disease. Probiotics attenuate and reverse gut dysbiosis to improve cardiovascular risk factors like hypertension and hypercholesterolemia. is a well-studied lactic acid-producing probiotic with known cholesterol-lowering properties and anti-inflammatory effects. Read More

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http://dx.doi.org/10.1152/ajpheart.00569.2019DOI Listing

Pressure-induced constriction of the middle cerebral artery is abolished in TrpC6 knockout mice.

Am J Physiol Heart Circ Physiol 2020 Jul 15;319(1):H42-H50. Epub 2020 May 15.

Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi.

Pressure-induced constriction (PIC) is an inherent response of small arteries and arterioles in which increases in intraluminal pressure evoke vasoconstriction. It is a critical mechanism of blood flow autoregulation in the kidney and brain. Degenerin (Deg) and transient receptor potential (Trp) protein families have been implicated in transduction of PIC because of evolutionary links to mechanosensing in the nematode and fly. Read More

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http://dx.doi.org/10.1152/ajpheart.00126.2020DOI Listing

Cardiac endurance training alters plasma profiles of circular RNA MBOAT2.

Am J Physiol Heart Circ Physiol 2020 Jul 15;319(1):H13-H21. Epub 2020 May 15.

Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany.

Marathon running is an extreme physical activity, which determines cardiopulmonary adaption of athletes. Circular RNAs (circRNAs) as potential biomarkers in the blood stream have so far not been tested after such strenuous activities. In silico approaches were performed to identify the potential candidate circRNA MBOAT2. Read More

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http://dx.doi.org/10.1152/ajpheart.00067.2020DOI Listing

Social isolation during the COVID-19 pandemic can increase physical inactivity and the global burden of cardiovascular disease.

Am J Physiol Heart Circ Physiol 2020 06 15;318(6):H1441-H1446. Epub 2020 May 15.

Applied Physiology and Nutrition Research Group, School of Physical Education and Sport, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil.

Emerging data indicate a substantial decrease in global physical activity levels during the period of social isolation adopted worldwide to contain the spread of the coronavirus disease 2019 (COVID-19). Confinement-induced decreases in physical activity levels and increases in sedentary behavior may provoke a rapid deterioration of cardiovascular health and premature deaths among populations with increased cardiovascular risk. Even short-term (1-4 wk) inactivity has been linked with detrimental effects in cardiovascular function and structure and increased cardiovascular risk factors. Read More

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http://dx.doi.org/10.1152/ajpheart.00268.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303725PMC

Chemogenetic activation of intracardiac cholinergic neurons improves cardiac function in pressure overload-induced heart failure.

Am J Physiol Heart Circ Physiol 2020 Jul 15;319(1):H3-H12. Epub 2020 May 15.

Department of Pharmacology and Physiology, George Washington University, Washington, District of Columbia.

Heart failure (HF) is characterized by autonomic imbalance with sympathetic hyperactivity and loss of parasympathetic tone. Intracardiac ganglia (ICG) neurons represent the final common pathway for vagal innervation of the heart and strongly regulate cardiac functions. This study tests whether ICG cholinergic neuron activation mitigates the progression of cardiac dysfunction and reduces mortality that occurs in HF. Read More

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http://dx.doi.org/10.1152/ajpheart.00150.2020DOI Listing

Cytosolic DNA sensor cGAS plays an essential pathogenetic role in pressure overload-induced heart failure.

Am J Physiol Heart Circ Physiol 2020 06 8;318(6):H1525-H1537. Epub 2020 May 8.

Department of Cardiology, Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Center for Cardiovascular Translational Research, Peking University People's Hospital, Beijing, China.

Growing evidence shows that activation of inflammation in the heart provokes left ventricular (LV) remodeling and dysfunction in humans and experimental animals with heart failure (HF). Moreover, recent studies found that cyclic GMP-AMP synthase (cGAS), serving as a cytosolic DNA sensor, was essential for activating innate immunity against infection and cellular damage by initiating the STING-IRFs-type I IFN signaling cascade, which played important roles in regulating the inflammatory response. However, the pathophysiological role of cGAS in pressure overload-induced HF is unclear. Read More

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http://dx.doi.org/10.1152/ajpheart.00097.2020DOI Listing

Atypical ALPK2 kinase is not essential for cardiac development and function.

Am J Physiol Heart Circ Physiol 2020 06 8;318(6):H1509-H1515. Epub 2020 May 8.

Department of Medicine, University of California, San Diego, La Jolla, California.

Protein kinases play an integral role in cardiac development, function, and disease. Recent experimental and clinical data have implied that protein kinases belonging to a family of atypical α-protein kinases, including α-protein kinase 2 (ALPK2), are important for regulating cardiac development and maintaining function via regulation of WNT signaling. A recent study in zebrafish reported that loss of ALPK2 leads to severe cardiac defects; however, the relevance of ALPK2 has not been studied in a mammalian animal model. Read More

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http://dx.doi.org/10.1152/ajpheart.00249.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311700PMC

Reduced Na current in Purkinje fibers explains cardiac conduction defects and arrhythmias in Duchenne muscular dystrophy.

Am J Physiol Heart Circ Physiol 2020 06 8;318(6):H1436-H1440. Epub 2020 May 8.

Department of Neurophysiology-Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.

Cardiac arrhythmias significantly contribute to mortality in Duchenne muscular dystrophy (DMD), a degenerative muscle disease triggered by mutations in the gene encoding for the intracellular protein dystrophin. A major source for the arrhythmias in patients with DMD is impaired ventricular impulse conduction, which predisposes for ventricular asynchrony, decreased cardiac output, and the development of reentrant mechanisms. The reason for ventricular conduction impairments and the associated arrhythmias in the dystrophic heart has remained unidentified. Read More

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http://dx.doi.org/10.1152/ajpheart.00224.2020DOI Listing

Exercise training ameliorates cerebrovascular dysfunction in a murine model of Alzheimer's disease: role of the P2Y2 receptor and endoplasmic reticulum stress.

Am J Physiol Heart Circ Physiol 2020 06 8;318(6):H1559-H1569. Epub 2020 May 8.

Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, Houston, Texas.

Cerebrovascular dysfunction is a critical risk factor for the pathogenesis of Alzheimer's disease (AD). The purinergic P2Y2 receptor and endoplasmic reticulum (ER) stress are tightly associated with vascular dysfunction and the pathogenesis of AD. However, the protective effects of exercise training on P2Y2 receptor- and ER stress-associated cerebrovascular dysfunction in AD are mostly unknown. Read More

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http://dx.doi.org/10.1152/ajpheart.00129.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311699PMC

Contractile work directly modulates mitochondrial protein levels in human engineered heart tissues.

Am J Physiol Heart Circ Physiol 2020 06 8;318(6):H1516-H1524. Epub 2020 May 8.

Department of Biomedical Engineering, Yale University, New Haven, Connecticut.

Engineered heart tissues (EHTs) have emerged as a robust in vitro model to study cardiac physiology. Although biomimetic culture environments have been developed to better approximate in vivo conditions, currently available methods do not permit full recapitulation of the four phases of the cardiac cycle. We have developed a bioreactor which allows EHTs to undergo cyclic loading sequences that mimic in vivo work loops. Read More

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http://dx.doi.org/10.1152/ajpheart.00055.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311697PMC

Using 4-vinylcyclohexene diepoxide as a model of menopause for cardiovascular disease.

Am J Physiol Heart Circ Physiol 2020 06 8;318(6):H1461-H1473. Epub 2020 May 8.

Department of Physiology, University of Arizona, Tucson, Arizona.

There is a sharp rise in cardiovascular disease (CVD) risk and progression with the onset of menopause. The 4-vinylcyclohexene diepoxide (VCD) model of menopause recapitulates the natural, physiological transition through perimenopause to menopause. We hypothesized that menopausal female mice were more susceptible to CVD than pre- or perimenopausal females. Read More

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http://dx.doi.org/10.1152/ajpheart.00555.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311698PMC

Reduced stiffness and augmented traction force in type 2 diabetic coronary microvascular smooth muscle.

Am J Physiol Heart Circ Physiol 2020 06 1;318(6):H1410-H1419. Epub 2020 May 1.

Center for Cardiovascular Research, The Heart Center, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio.

Type 2 diabetic (T2DM) coronary resistance microvessels (CRMs) undergo inward hypertrophic remodeling associated with reduced stiffness and reduced coronary blood flow in both mice and pig models. Since reduced stiffness does not appear to be due to functional changes in the extracellular matrix, this study tested the hypothesis that decreased CRM stiffness in T2DM is due to reduced vascular smooth muscle cell (VSMC) stiffness, which impacts the traction force generated by VSMCs. Atomic force microscopy (AFM) and traction force microscopy (TFM) were conducted on primary low-passage CRM VSMCs from normal / and T2DM / mice in addition to low-passage normal and T2DM deidentified human coronary VSMCs. Read More

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http://dx.doi.org/10.1152/ajpheart.00542.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311703PMC

Does vascular stiffness predict white matter hyperintensity burden in ischemic heart disease with preserved ejection fraction?

Am J Physiol Heart Circ Physiol 2020 06 1;318(6):H1401-H1409. Epub 2020 May 1.

School of Kinesiology, Western University, London, Ontario, Canada.

The survival rate of patients with ischemic heart disease (IHD) is increasing. However, survivors experience increased risk for neurological complications. The mechanisms for this increased risk are unknown. Read More

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http://dx.doi.org/10.1152/ajpheart.00057.2020DOI Listing

Differential effects of REV-ERBα/β agonism on cardiac gene expression, metabolism, and contractile function in a mouse model of circadian disruption.

Am J Physiol Heart Circ Physiol 2020 06 1;318(6):H1487-H1508. Epub 2020 May 1.

Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

Cell-autonomous circadian clocks have emerged as temporal orchestrators of numerous biological processes. For example, the cardiomyocyte circadian clock modulates transcription, translation, posttranslational modifications, ion homeostasis, signaling cascades, metabolism, and contractility of the heart over the course of the day. Circadian clocks are composed of more than 10 interconnected transcriptional modulators, all of which have the potential to influence the cardiac transcriptome (and ultimately cardiac processes). Read More

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http://dx.doi.org/10.1152/ajpheart.00709.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311693PMC
June 2020
3.838 Impact Factor