Can Intestinal Microbiota and Circulating Microbial Products Contribute to Pulmonary Arterial Hypertension?
Abstract Pulmonary arterial hypertension (PAH) is a fatal disease with a median survival of only 5-7 years. PAH is characterized by remodeling of the pulmonary vasculature causing reduced pulmonary arterial compliance (PAC) and increased pulmonary vascular resistance (PVR), ultimately resulting in right ventricular failure and death. Better therapies for PAH will require a paradigm shift in our understanding of the early pathophysiology. PAC decreases before there is an increase in the PVR. Unfortunately, current treatment has little effect on PAC. The loss of compliance correlates with extracellular matrix remode...
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 6, 2019 Category: Physiology Authors: Thenappan T, Khoruts A, Chen Y, Weir EK Tags: Am J Physiol Heart Circ Physiol Source Type: research

Renal denervation improves sodium excretion in rats with chronic heart failure: Effects on expression of renal ENaC and AQP2.
Abstract Previously we have shown that increased expression of renal epithelial sodium channels (ENaC) may contribute to the renal sodium and water retention observed during chronic heart failure (CHF). The goal of this study was to examine whether renal denervation (RDN) changed the expressions of renal sodium transporters ENaC, sodium-hydrogen exchanger-3 proteins (NHE3), and water channel aquaporin 2 (AQP2) in rats with CHF. CHF was produced by left coronary artery ligation in rats. Four weeks after ligation surgery, surgical bilateral RDN were performed. The expression of ENaC, NHE3 and AQP2 in both renal cort...
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 6, 2019 Category: Physiology Authors: Zheng H, Liu X, Katsurada K, Patel KP Tags: Am J Physiol Heart Circ Physiol Source Type: research

Effects of prolonged type 2 diabetes on mitochondrial function in cerebral blood vessels.
In conclusion, prolonged dietary diabetes leads to stabilization, rather than deterioration of metabolic status in the cerebral circulation, despite continued overproduction of ROS. PMID: 31490734 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 6, 2019 Category: Physiology Authors: Merdzo I, Rutkai I, Sure VNLR, Katakam PVG, Busija DW Tags: Am J Physiol Heart Circ Physiol Source Type: research

Reconstitution of autophagy ameliorates vascular function and arterial stiffening in spontaneously hypertensive rats.
Abstract Insufficient autophagy has been proposed as a mechanism of cellular aging, as this leads to the accumulation of dysfunctional macromolecules and organelles. Premature vascular aging occurs in hypertension. In fact, many factors that contribute to the deterioration of vascular function as we age are accelerated in clinical and experimental hypertension. Previously, we have reported decreased autophagy in arteries from spontaneously hypertensive rats (SHR); however, the effects of restoring autophagic activity on blood pressure and vascular function are currently unknown. We hypothesized that reconstitution...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 30, 2019 Category: Physiology Authors: McCarthy CG, Wenceslau CF, Calmasini FB, Klee NS, Brands MW, Joe B, Webb RC Tags: Am J Physiol Heart Circ Physiol Source Type: research

The gut microbiome and atherosclerosis: current knowledge and clinical potential.
Abstract Cardiovascular disease (CVD) is the leading cause of death worldwide. The human body is populated by a diverse community of microbes, dominated by bacteria, but also including viruses and fungi. The largest and most complex of these communities is located in the gastrointestinal system and with their associated genome, are known as the gut microbiome. Gut microbiome perturbations and related dysbiosis have been implicated in the progression and pathogenesis of CVD, including atherosclerosis, hypertension and heart failure. Although there have been advances in the characterisation and analysis of the gut m...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 30, 2019 Category: Physiology Authors: Ahmad A, Dwivedi G, O'Gara F, Caparros-Martin J, Ward N Tags: Am J Physiol Heart Circ Physiol Source Type: research

Long non-coding RNA LINC00342 promotes growth of infantile hemangioma by sponging miR-3619-5p from HDGF.
Abstract Infantile hemangiomas (IH) are a type of benign vascular neoplasms, which may cause permanent scarring. Hemangioma-derived endothelial cells (HemECs) are commonly used as an in vitro model to study IH. Long non-coding RNA (lncRNA) is a type of RNA transcripts longer than 200 nucleotides which do not encode any protein. LINC00342 was discovered to regulate proliferation and apoptosis in non-small cell lung cancer. However, the role of LINC00342 in IH has never been reported before. Expressions of LINC00342 and miR-3619-5p were detected in proliferating versus normal skin tissues. Colony formation and CCK-8...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 30, 2019 Category: Physiology Authors: Liu Z, Kang Z, Dai Y, Zheng H, Wang Y Tags: Am J Physiol Heart Circ Physiol Source Type: research

Preeminent Role of the Cardiorenal Axis in the Antihypertensive Response to an Arteriovenous Fistula: An In Silico Analysis.
Abstract Percutaneous creation of a small central arteriovenous (AV) fistula is currently being evaluated for the treatment of uncontrolled hypertension (HT). Although the mechanisms that contribute to the antihypertensive effects of the fistula are unclear, investigators have speculated that chronic blood pressure (BP) lowering may be due to: 1) reduced total peripheral resistance (TPR), 2) increased secretion of atrial natriuretic peptide (ANP), and/or 3) suppression of renal sympathetic nerve activity (RSNA). We used an established integrative mathematical model of human physiology to investigate these possibil...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 30, 2019 Category: Physiology Authors: Clemmer JS, Pruett WA, Hester RL, Lohmeier TE Tags: Am J Physiol Heart Circ Physiol Source Type: research

Investigation of the mechanisms of cyclooxygenase-mediated mechanoreflex sensitization in a rat model of simulated peripheral artery disease.
Abstract Mechanical and metabolic stimuli within contracting skeletal muscles reflexly increase sympathetic nervous system activity and blood pressure. That reflex, termed the exercise pressor reflex, is exaggerated in peripheral artery disease (PAD) patients and in a rat PAD model with a chronically ligated femoral artery. The cyclooxygenase (COX) pathway contributes to the exaggerated pressor response during rhythmic skeletal muscle contractions in PAD patients but the specific mechanism(s) of the COX-mediated exaggeration is not known. In decerebrate, unanesthetized rats with a chronically ligated femoral arter...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 30, 2019 Category: Physiology Authors: Butenas ALE, Hopkins TD, Rollins KS, Felice KP, Copp SW Tags: Am J Physiol Heart Circ Physiol Source Type: research

c-Kit Suppresses Atherosclerosis in Hyperlipidemic Mice.
Abstract Atherosclerosis is the most common underlying cause of cardiovascular morbidity and mortality worldwide. c-Kit (CD117) is a member of the receptor tyrosine kinase family, which regulates differentiation, proliferation, and survival of multiple cell types. Recent studies have shown that c-Kit and its ligand stem cell factor (SCF) are present in arterial endothelial cells and smooth muscle cells (SMCs). The role of c-Kit in cardiovascular disease remains unclear. The aim of the current study is to determine the role of c-Kit in atherogenesis. For this purpose, atherosclerotic plaques were quantified in c-Ki...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 23, 2019 Category: Physiology Authors: Song L, Zigmond Z, Martinez L, Lassance-Soares RM, Macias AE, Velazquez OC, Liu ZJ, Salama A, Webster KA, Vazquez-Padron RI Tags: Am J Physiol Heart Circ Physiol Source Type: research

Inflammation in non-ischemic heart disease: initiation by cardiomyocyte CaMKII and NLRP3 inflammasome signaling.
Abstract There is substantial evidence that chronic heart failure in humans and in animal models is associated with inflammation. Ischemic interventions such as myocardial infarction (MI) lead to necrotic cell death and release of damage associated molecular patterns (DAMPs), factors that signal cell damage and induce expression of pro-inflammatory chemokines and cytokines. It has recently become evident that non-ischemic interventions are also associated with increases in inflammatory genes and immune cell accumulation in the heart and that these contribute to fibrosis and ventricular dysfunction. How pro-inflamm...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 23, 2019 Category: Physiology Authors: Suetomi T, Miyamoto S, Brown JH Tags: Am J Physiol Heart Circ Physiol Source Type: research

Cortical bone derived stem-cell therapy reduces apoptosis after myocardial infarction.
Abstract Ischemic heart diseases like myocardial infarction are the largest contributors to cardiovascular disease world-wide. The resulting cardiac cell death impairs function of the heart and can lead to heart failure and death. Reperfusion of the ischemic tissue is necessary but causes damage to the surrounding tissue by re-perfusion injury. Cortical bone stem cells (CBSCs) have been shown to increase pump function and decrease scar size in a large animal swine model of myocardial infarction (MI). To investigate the potential mechanism for these changes, we hypothesized that CBSCs were altering cardiac cell dea...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 23, 2019 Category: Physiology Authors: Hobby AR, Sharp Iii TE, Berretta RM, Borghetti G, Feldsott E, Mohsin S, Houser SR Tags: Am J Physiol Heart Circ Physiol Source Type: research

Absence of Gravin Mediated Signaling Inhibits Development of High Fat Diet-Induced Hyperlipidemia and Atherosclerosis.
Abstract Gravin, an A-kinase anchoring protein (AKAP), is known to play a role in regulating key processes that lead to inflammation and atherosclerosis development; namely, cell migration, proliferation, and apoptosis. We investigated the role of gravin in the development of high-fat-diet (HFD) induced atherosclerosis and hyperlipidemia. Five-week-old male wild-type (WT) and gravin-t/t mice were fed normal-diet (ND) or HFD for 16-weeks. Gravin-t/t mice showed significantly lower liver-to-body-weight ratio, cholesterol, triglyceride, and very low-density lipoprotein levels in serum as compared to WT mice on HFD. F...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 23, 2019 Category: Physiology Authors: Fan Q, Yin X, Rababa'h A, Diaz Diaz A, Wijaya CS, Singh S, Suryavanshi SV, Vo HH, Saeed M, Zhang Y, McConnell BK Tags: Am J Physiol Heart Circ Physiol Source Type: research

Global reach 2018: reduced flow-mediated dilation stimulated by sustained increases in shear stress in high-altitude excessive erythrocytosis.
GLOBAL REACH 2018: REDUCED FLOW-MEDIATED DILATION STIMULATED BY SUSTAINED INCREASES IN SHEAR STRESS IN HIGH-ALTITUDE EXCESSIVE ERYTHROCYTOSIS. Am J Physiol Heart Circ Physiol. 2019 Aug 23;: Authors: Tremblay JC, Coombs GB, Howe CA, Vizcardo-Galindo G, Figueroa-Mujica RJ, Bermudez D, Tymko MM, Villafuerte FC, Ainslie PN, Pyke KE Abstract Excessive erythrocytosis (EE; hemoglobin concentration [Hb] ≥21 g dl-1 in adult males) is a maladaptive high-altitude pathology associated with increased cardiovascular risk and reduced reactive hyperemia flow-mediated dilation; however, whether a similar impairment...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 23, 2019 Category: Physiology Authors: Tremblay JC, Coombs GB, Howe CA, Vizcardo-Galindo G, Figueroa-Mujica RJ, Bermudez D, Tymko MM, Villafuerte FC, Ainslie PN, Pyke KE Tags: Am J Physiol Heart Circ Physiol Source Type: research

Aortic distensibility is associated with both resting and hyperemic coronary blood flow.
This study compared invasive measures of coronary blood flow (CBF) with cardiac magnetic resonance (CMR) derived aortic distensibility (AD). METHODS: Following coronary angiography, a Doppler FloWire and infusion microcatheter were advanced into the study vessel. Average peak velocity (APV) was acquired at baseline and following intracoronary adenosine to derive coronary flow velocity reserve (CFVR = hyperemic APV/resting APV), and CBF (π x [Diameter]2 x APV x 0.125). Following angiography, patients underwent CMR to evaluate distensibility at the ascending aorta (AA), proximal descending aorta (PDA) and distal desc...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 23, 2019 Category: Physiology Authors: Nelson AJ, Puri R, Nicholls SJ, Dundon BK, Richardson JD, Sidharta SL, Teo KS, Worthley SG, Worthley M Tags: Am J Physiol Heart Circ Physiol Source Type: research

Modelling arterial pulse waves in healthy ageing: a database for in silico evaluation of haemodynamics and pulse wave indices.
In conclusion, the publicly available PW database (DOI: 10.5281/zenodo.2633175) is a valuable resource for understanding CV determinants of PWs, and for the development and pre-clinical assessment of PW analysis algorithms. It is particularly useful because the exact CV properties which generated each PW are known. PMID: 31442381 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 23, 2019 Category: Physiology Authors: Charlton P, Mariscal Harana J, Vennin S, Li Y, Chowienczyk P, Alastruey J Tags: Am J Physiol Heart Circ Physiol Source Type: research

Exosomes derived from Induced Vascular Progenitor Cells Promote Angiogenesis in vitro and in an in vivo Rat Hindlimb Ischemia Model.
Abstract Induced vascular progenitor cells (iVPCs) were created as an ideal cell type for regenerative medicine and have been reported to positively promote collateral blood flow and improve cardiac function in a rat model of myocardial ischemia. Exosomes have emerged as a novel biomedicine that mimics the function of the donor cells. We investigated the angiogenic activity of exosomes from induced vascular progenitor cells (iVPC-Exo) as a cell-free therapeutic approach for ischemia. Exosomes from iVPCs and rat aortic endothelial cells (RAECs) were isolated using a combination of ultrafiltration and size-exclusion...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 16, 2019 Category: Physiology Authors: Johnson TK, Zhao L, Zhu D, Wang Y, Xiao Y, Oguljahan B, Zhao X, Kirlin WG, Yin L, Chilian WM, Liu D Tags: Am J Physiol Heart Circ Physiol Source Type: research

Guidelines for evaluating myocardial cell death.
sui T Abstract Cell death is a fundamental process in cardiac pathologies. Recent studies revealed multiple forms of cell death, and several of them have been demonstrated to underlie adverse cardiac remodeling and heart failure. With the expansion in the area of myocardial cell death and increasing concerns over rigor and reproducibility, it is important and timely to set a guideline for the best practices of evaluating myocardial cell death. There are six major forms of regulated cell death observed in cardiac pathologies namely apoptosis, necroptosis, mitochondrial-mediated necrosis, pyroptosis, ferroptosis, an...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 16, 2019 Category: Physiology Authors: Mishra PK, Adameová A, Hill JA, Baines CP, Kang PM, Downey J, Narula J, Takahashi M, Abbate A, Piristine HC, Kar S, Su S, Higa JK, Kawasaki NK, Matsui T Tags: Am J Physiol Heart Circ Physiol Source Type: research

-Cardiac intramural electrical mapping reveals focal delays but no conduction velocity slowing in the peri-infarct region.
This study characterises, for the first time, the intramural spread of electrical activation in the peri-infarct region of chronic reperfusion MIs. Four sheep were studied 13 weeks after antero-apical reperfusion infarction. Extracellular potentials (ECPs) were recorded in a ~20×20 mm2 region adjacent to the infarct boundary (25 plunge needles
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 16, 2019 Category: Physiology Authors: Trew ML, Engelman ZJ, Caldwell BJ, Lever NA, LeGrice IJ, Smaill BH Tags: Am J Physiol Heart Circ Physiol Source Type: research

Placental Growth Factor Levels in Quadriceps Muscle Are Reduced by a Western Diet in Association With Advanced Glycation End Products.
Abstract In peripheral artery disease (PAD), atherosclerotic occlusion chronically impairs limb blood flow. Arteriogenesis (collateral artery remodeling) is a vital adaptive response to PAD that protects tissue from ischemia. Type II diabetics have a high risk of developing PAD, and would benefit from arteriogenesis. However, arteriogenesis is suppressed in diabetics by a multifaceted mechanism which remains incompletely defined. Upregulation of placental growth factor (PLGF) is a key early step in arteriogenesis. Therefore, we hypothesized that metabolic dysfunction would impair PLGF expression in skeletal muscle...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 9, 2019 Category: Physiology Authors: Silva AT, Rouf F, Semola OA, Payton ME, Lovern PC Tags: Am J Physiol Heart Circ Physiol Source Type: research

Role of B1 and B2 Lymphocytes in Placental Ischemia-induced Hypertension.
Abstract Preeclampsia is a prevalent pregnancy complication characterized by new-onset maternal hypertension and inflammation, with placental ischemia as the initiating event. Studies of others have provided evidence for the importance of lymphocytes in placental ischemia-induced hypertension, however contributions of B1 vs. B2 lymphocytes are unknown. We hypothesized that peritoneal B1 lymphocytes are important for placental ischemia-induced hypertension. As an initial test of this hypothesis, the effect of anti-CD20 depletion on both B cell populations was determined in Reduced Utero-placental Perfusion Pressure...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 9, 2019 Category: Physiology Authors: Laule CF, Odean EJ, Wing CR, Root KM, Towner KJ, Hamm CM, Gilbert JS, Fleming SD, Regal JF Tags: Am J Physiol Heart Circ Physiol Source Type: research

Racial Disparities in Cardiovascular Disease Risk: Mechanisms of Vascular Dysfunction.
Abstract Cardiovascular disease (CVD) accounts for a third of all deaths in the United States making it the leading cause of morbidity and mortality. While CVD affects individuals of all races / ethnicities, the prevalence of CVD is highest in non-hispanic black individuals (BL) relative to other populations. The mechanism(s) responsible for elevated CVD risk in the BL population remains incompletely understood. However, impaired vascular vasodilator capacity and exaggerated vascular vasoconstrictor responsiveness are likely contributing factors, both of which are present even in young otherwise healthy BL. Within...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 9, 2019 Category: Physiology Authors: Brothers RM, Fadel PJ, Keller DM Tags: Am J Physiol Heart Circ Physiol Source Type: research

Detrimental Effects of Chemotherapy on Human Coronary Microvascular Function.
CONCLUSIONS: In vessels from adult subjects, acute treatment with Dox in clinically relevant doses caused significant impairment of coronary arteriolar function, whereas vessels from pediatric subjects showed only marginal impairment to the same stressor. This interesting finding might explain the delayed onset of future adverse CV events in children compared to adults after anthracycline therapy. PMID: 31397169 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 9, 2019 Category: Physiology Authors: Hader SN, Zinkevich NS, Norwood Toro LE, Kriegel AJ, Kong A, Freed JK, Gutterman DD, Beyer AM Tags: Am J Physiol Heart Circ Physiol Source Type: research

High-mannose intercellular adhesion molecule-1 (ICAM-1) enhances CD16+ monocyte adhesion to the endothelium.
Abstract Human monocytes have been classified into three distinct groups - classical (anti-inflammatory; CD14+/CD16-), non-classical (patrolling; CD14+/CD16++), and intermediate (pro-inflammatory; CD14++/CD16+). Adhesion of non-classical / intermediate monocytes with the endothelium is important for innate immunity, and also vascular inflammatory disease. However, there is an incomplete understanding of the mechanisms that regulate CD16+ vs. CD16- monocyte adhesion to the inflamed endothelium. Here, we tested the hypothesis that a high mannose (HM) N-glycoform of intercellular adhesion molecule-1 (ICAM-1) on the e...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 9, 2019 Category: Physiology Authors: Regal-McDonald K, Xu B, Barnes JW, Patel RP Tags: Am J Physiol Heart Circ Physiol Source Type: research

Hyperphosphatemia is Required for Initiation, but not Propagation, of Kidney Failure-Induced Calcific Aortic Valve Disease.
Abstract High serum levels of phosphate are associated with uraemia-induced calcific aortic valve disease (CAVD). However, it is not clear whether hyperphosphataemia is required in all phases of the process. Our aim was to determine the effects of phosphate and phosphate depletion at different phases of valve disease. The experimental design consisted of administering a uraemia-inducing diet, with or without phosphate enrichment, to rats for 7 weeks. Forty-two rats were fed with a phosphate-enriched uraemic regimen that caused renal insufficiency and hyperphosphataemia. Another 42 rats were fed with a phosphate-de...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 9, 2019 Category: Physiology Authors: Shuvy M, Abedat S, Eliaz R, Abu-Rmeileh I, Abu-Snieneh A, Ben Dov IZ, Meir K, Pereg D, Beeri R, Lotan C Tags: Am J Physiol Heart Circ Physiol Source Type: research

ATP-dependent chromatin remodeling complexes in embryonic vascular development and hypertension.
Abstract Hypertension, a chronic elevation in blood pressure, is the largest single contributing factor to mortality worldwide and the most common preventable risk factor for cardiovascular disease. High blood pressure increases the risk for someone to experience a number of adverse cardiovascular events including heart failure, stroke, or aneurysm. Despite advancements in understanding factors that contribute to hypertension, the etiology remains elusive and there remains a critical need to develop innovative study approaches in order to develop more effective therapeutics. ATP-dependent chromatin remodelers are ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 9, 2019 Category: Physiology Authors: Crosswhite PL Tags: Am J Physiol Heart Circ Physiol Source Type: research

Right Ventricular Oxygen Delivery as a Determinant of Right Ventricular Functional Reserve during Exercise in Juvenile Swine with Chronic Pulmonary Hypertension.
In this study, we aim to establish RV-oxygen (O2) deliveryas a determinant for RV-functional reserve during exercise in swine with chronic PH. METHODS AND RESULTS: Chronic PH was induced by pulmonary vein banding (PVB), with sham operation serving as control. RV function and RV-O2delivery were measured over time in chronically instrumented swine, up to 12 weeks after PVB at rest and during exercise. At rest, RV afterload (pulmonary artery pressure and Ea) and contractility (Ees and dP/dtmax) were higher in PH compared with control with preserved cardiac index and RV-O2delivery. However, RV-functional reserve, as measu...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 9, 2019 Category: Physiology Authors: Cai Z, van Duin RWB, Stam K, Uitterdijk A, van der Velden J, Vonk-Noordegraaf A, Duncker DJ, Merkus D Tags: Am J Physiol Heart Circ Physiol Source Type: research

Optimized Protocols for Isolation, Fixation and Flow Cytometric Characterization of Leukocytes in Ischemic Hearts.
Abstract Immune activation post-myocardial infarction is an orchestrated sequence of cellular responses to effect tissue repair and healing. However, excessive and dysregulated inflammation can result in left ventricular remodeling and pathological alterations in the structural and mechanical attributes of the heart. Identification of key pathways and critical cellular mediators of inflammation is thus essential to design immunomodulatory therapies for myocardial infarction and ischemic heart failure. Despite this, the experimental approaches to isolate mononuclear cells from the heart are diverse, and detailed pr...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 2, 2019 Category: Physiology Authors: Covarrubias R, Ismahil MA, Rokosh G, Hamid T, Accornero F, Singh H, Gumina RJ, Prabhu S, Bansal S Tags: Am J Physiol Heart Circ Physiol Source Type: research

Asynchronous action potential discharge in human muscle sympathetic nerve activity.
Abstract What strategies are employed by the sympathetic system to communicate with the circulation? Muscle sympathetic nerve activity (MSNA) occurs in bursts of synchronous action potential (AP) discharge, yet whether between-burst asynchronous AP firing exists remains unknown. Using multi-unit microneurography and a continuous wavelet transform to isolate APs, we studied AP synchronicity within human MSNA. Asynchronous APs were defined as those which occurred between bursts. Experiment One quantified AP synchronicity in eight individuals at baseline (BSL), -10 mmHg lower body negative pressure (LBNP), -40 mmHg L...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 2, 2019 Category: Physiology Authors: Klassen SA, Moir ME, Limberg JK, Baker SE, Nicholson WT, Curry TB, Joyner MJ, Shoemaker JK Tags: Am J Physiol Heart Circ Physiol Source Type: research

Cardiac Troponin I Phosphorylation Underlies Myocardial Contractile Dysfunction Induced by Hypothermia-Rewarming.
Abstract Rewarming the intact heart after a period of hypothermia is associated with reduced myocardial contractility, decreased Ca2+ sensitivity and increased cardiac troponin I (cTnI) phosphorylation. We hypothesized that hypothermia/rewarming (H/R) induces left ventricular (LV) contractile dysfunction due to phosphorylation of cTnI at Ser 23/24. To test this hypothesis, the response of wildtype mice (n=7) to H/R was compared to transgenic mice expressing slow skeletal TnI (TG-ssTnI; n=7) that lacks the Ser 23/24 phosphorylation sites. Hypothermia was induced by surface cooling and maintained at 23-25ºC for...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 2, 2019 Category: Physiology Authors: Tveita T, Arteaga GM, Han YS, Sieck GC Tags: Am J Physiol Heart Circ Physiol Source Type: research

Dilated cardiomyopathy mutation (R174W) in troponin T attenuates the length-mediated increase in crossbridge recruitment and myofilament Ca2+ sensitivity.
In this study, we investigated the effect of DCM-linked mutation (R173W) in human cardiac troponin T (TnT) on myofilament LDA. R173W mutation is associated with left ventricular dilatation and systolic dysfunction, and is found in multiple families. R173W mutation is in the central region (residues 80-180) of TnT, which is known to be important for myofilament cooperativity and crossbridge (XB) recruitment. Steady-state and dynamic contractile parameters were measured in detergent-skinned guinea pig left ventricular muscle fibers reconstituted with recombinant guinea pig wild-type TnT (TnTWT) or mutant TnT (TnTR174W; guine...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 2, 2019 Category: Physiology Authors: Reda SM, Chandra M Tags: Am J Physiol Heart Circ Physiol Source Type: research

Cardiac remodeling after six weeks of high-intensity interval training to exhaustion in endurance-trained males.
Brassard P Abstract High-intensity interval training (HIIT) improves physical performance of endurance athletes, although studies examining its cardiovascular effects are sparse. We evaluated the impact of HIIT on blood pressure, heart rate and cardiac cavities size and function in endurance-trained adults. Seventeen endurance-trained males underwent 24-hour ambulatory blood pressure monitoring (ABPM) and Doppler echocardiography at baseline and after 6 weeks of HIIT. Participants were divided in 2 groups (85% maximal aerobic power (MP); HIIT85, n=8 and 115% MP; HIIT115 , n = 9) in order to compare the impact of ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 26, 2019 Category: Physiology Authors: Mahjoub H, Le Blanc O, Paquette M, Imhoff S, Labrecque L, Drapeau A, Poirier P, Bédard É, Pibarot P, Brassard P Tags: Am J Physiol Heart Circ Physiol Source Type: research

Impact of heart rate on cross-bridge cycling kinetics in failing and non-failing human myocardium.
Abstract The force-frequency relationship (FFR) is an important regulatory mechanism that increases the force-generating capacity as well as the contraction and relaxation kinetics in human cardiac muscle as the heart rate increases. In human heart failure, the normally positive FFR often becomes flat, or even negative. The rate of cross-bridge cycling, which has been reported to affect cardiac output, could be potentially dysregulated and contribute to blunted or negative FFR in heart failure. We recently developed and here use a novel method for measuring the rate of tension redevelopment (ktr). This method allo...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 26, 2019 Category: Physiology Authors: Chung JH, Milani-Nejad N, Davis JP, Weisleder N, Whitson BA, Mohler PJ, Janssen PML Tags: Am J Physiol Heart Circ Physiol Source Type: research

Sarco/Endoplasmic Reticulum Ca2+-ATPase is a more effective calcium remover than Sodium-Calcium Exchanger in human embryonic stem cell-derived cardiomyocytes.
Abstract Human pluripotent stem cell (hPSCs)-derived ventricular (V) cardiomyocytes (CMs) display immature Ca2+-handing properties with smaller transient amplitudes and slower kinetics due to such differences in crucial Ca2+-handling proteins as the poor sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pumpbut robust Na-Ca exchanger (NCX) activities in human embryonic stem cell (ESC)-derived VCMs compared to adult. Despite their fundamental importance in excitation-contraction coupling, the relative contribution of SERCA and NCX to Ca2+-handling of hPSC-VCMs remains unexplored.We systematically altered the activiti...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 26, 2019 Category: Physiology Authors: Li S, Chopra A, Keung W, Chan C, Costa KD, Kong CW, Hajjar RJ, Chen C, Li R Tags: Am J Physiol Heart Circ Physiol Source Type: research

CORP: Practical Tools for Improving Experimental Design and Reporting of Laboratory Studies of Cardiovascular Physiology and Metabolism.
Abstract An exercise was undertaken to improve the quality of animal cardiac and metabolic studies at the Baker Heart and Diabetes Institute, Australia. The exercise consisted of: i) a short survey to acquire baseline data on current practices regarding the conduct of animal studies; ii) a series of presentations for promoting awareness, and providing advice and practical tools for improving experimental design; iii) a follow-up survey 12 months later to assess whether practices had changed. The surveys were compulsory for responsible investigators (N=16; paired data presented). Other investigators named on animal...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 26, 2019 Category: Physiology Authors: Weeks KL, Henstridge DC, Salim A, Shaw JE, Marwick TH, McMullen JR Tags: Am J Physiol Heart Circ Physiol Source Type: research

Monophasic Action Potential Amplitude for Substrate Mapping.
In this report, we perform cardiac mapping with monophasic action potential (MAP) amplitude. We hypothesize that MAP amplitude (MAPA) will provide more accurate infarct sizes than other mapping modalities via increased sensitivity to distinguish healthy myocardium from scar tissue. Methods Using the left-coronary artery ligation Sprague Dawley rat model of ischemic heart failure, we investigate the accuracy of in vivo ventricular epicardial maps derived from MAPA, MAP duration to 90% repolarization (MAPD90), unipolar voltage amplitude (UVA), and bipolar voltage amplitude (BVA) when compared to gold-standard histopathologic...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 26, 2019 Category: Physiology Authors: Chinyere IR, Hutchinson M, Moukabary T, Lancaster J, Goldman S, Juneman E Tags: Am J Physiol Heart Circ Physiol Source Type: research

Both gain and loss of Nampt function promote pressure-overload-induced heart failure.
Abstract The heart requires high energy production, but metabolic ability declines in the failing heart. Nicotinamide phosphoribosyl-transferase (Nampt) is a rate-limiting enzyme in the salvage pathway of NAD synthesis. NAD is directly involved in various metabolic processes and may indirectly regulate metabolic gene expression through Sirt1, an NAD-dependent protein deacetylase. However, how Nampt regulates cardiac function and metabolism in the failing heart is poorly understood. Here we show that pressure-overload (PO)-induced heart failure is exacerbated in both systemic Nampt heterozygous knockout (Nampt+/-) ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 26, 2019 Category: Physiology Authors: Byun J, Oka SI, Imai N, Huang CY, Ralda G, Zhai P, Ikeda Y, Ikeda S, Sadoshima J Tags: Am J Physiol Heart Circ Physiol Source Type: research

Can improvement in Hormonal and Energy balance Reverse Cardiovascular Risk Factors in Amenorrheic Athletes?
Abstract Female athletes display a high prevalence of hypothalamic amenorrhea as a result of energy imbalance. In these amenorrheic athletes, the decreased luteinizing hormone / follicular stimulating hormone secretion leads to deficiency in endogenous estrogen. The severe estrogen deficiency in these athletes may increase cardiovascular risk similar to that in post-menopausal women. This review discusses the potential cardiovascular risk factors in amenorrheic athletes as a result of hypoestrogenism, which include endothelial dysfunction and unfavourable lipid profile. We also consider the potential to reverse th...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 19, 2019 Category: Physiology Authors: Grosman-Rimon L, Wright E, Freedman D, Kachel E, Hui S, Epstein I, Eilat-Adar S, Gutterman DD Tags: Am J Physiol Heart Circ Physiol Source Type: research

CD8+ T-cells Negatively Regulate Inflammation Post-Myocardial Infarction.
In conclusion, despite having improved cardiac physiology and overall survival, CD8atm1Mak mice had increased innate inflammation and poor scar formation leading to higher incidence of cardiac rupture. Our data suggest that the role of CD8+ T-cells in post-MI recovery may be both beneficial and detrimental to cardiac remodeling and is mediated via a cell-specific mechanism. PMID: 31322426 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 19, 2019 Category: Physiology Authors: Ilatovskaya DV, Pitts C, Clayton J, Domondon M, Troncoso M, Pippin S, DeLeon-Pennell KY Tags: Am J Physiol Heart Circ Physiol Source Type: research

Premature ventricular contractions activate vagal afferents and alter autonomic tone: implications for premature ventricular contraction-induced cardiomyopathy.
Abstract Mechanisms behind development of premature ventricular contraction (PVC)-induced cardiomyopathy remain unclear. PVCs may adversely modulate the autonomic nervous system to promote development of heart failure. Afferent neurons in the inferior vagal (nodose) ganglia transduce cardiac activity and modulate parasympathetic output.Effects of PVCs on cardiac parasympathetic efferent and afferent neurotransmission are unknown. The purpose of this study was to evaluate effects of PVCs on parasympathetic afferent neurotransmission and compare these effects to a known powerful autonomic modulator, myocardial ische...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 19, 2019 Category: Physiology Authors: Salavatian S, Yamaguchi N, Hoang JD, Lin N, Patel S, Ardell JL, Armour JA, Vaseghi M Tags: Am J Physiol Heart Circ Physiol Source Type: research

Reversal of heart failure in a chemogenetic model of persistent cardiac redox stress.
Abstract We previously described a novel "chemogenetic" animal model of heart failure that recapitulates a characteristic feature commonly found in human heart failure: chronic oxidative stress. This heart failure model uses a chemogenetic approach to activate a recombinant yeast D-amino acid oxidase in rat hearts in vivo in order to generate oxidative stress, which then rapidly leads to the development of a dilated cardiomyopathy. Here we apply this new model to drug testing by studying its response to treatment with the angiotensin-II (Ang-II) receptor blocker valsartan, administered either alone or wi...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 12, 2019 Category: Physiology Authors: Sorrentino A, Steinhorn B, Troncone L, Saravi SS, Badole SL, Eroglu E, Kijewski MF, Divakaran S, Di Carli M, Michel T Tags: Am J Physiol Heart Circ Physiol Source Type: research

DNA Methylation Reprograms Cardiac Metabolic Gene Expression in End-Stage Human Heart Failure.
Abstract Heart Failure (HF) is a leading cause of morbidity and mortality in the United States and worldwide. As a multifactorial syndrome with unpredictable clinical outcomes, identifying the common molecular underpinnings that drive HF pathogenesis remains a major focus of investigation. Disruption of cardiac gene expression has been shown to mediate a common final cascade of pathological hallmarks, wherein the heart reactivates numerous developmental pathways. Although the central regulatory mechanisms that drive this cardiac transcriptional reprogramming remain unknown, epigenetic contributions are likely. In ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 12, 2019 Category: Physiology Authors: Pepin ME, Drakos S, Ha CM, Tristani-Firouzi M, Selzman CH, Fang JC, Wende AR, Wever-Pinzon O Tags: Am J Physiol Heart Circ Physiol Source Type: research

Drug eluting stent specifically designed to target vascular smooth muscle cell phenotypic modulation attenuated restenosis through YAP pathway.
CONCLUSIONS: We demonstrated that SFES attenuated in-stent restenosis through YAP-mediated SMC phenotypic modulation. Targeting SMC phenotypic modulation by drug eluting stent (DES) represents an attractive therapeutic approach for the treatment of occlusive vascular diseases. PMID: 31298560 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 12, 2019 Category: Physiology Authors: Huang C, Zhang W, Zhu Y Tags: Am J Physiol Heart Circ Physiol Source Type: research

Intravenous ivabradine augments the dynamic heart rate response to moderate vagal nerve stimulation in anesthetized rats.
Abstract Ivabradine is a selective bradycardic agent that reduces the heart rate (HR) by inhibiting the hyperpolarization-activated cyclic nucleotide-gated channels. Although its cardiovascular effect is thought to be minimal except inducing bradycardia, ivabradine could interact with cardiovascular regulation by the autonomic nervous system. We tested whether ivabradine modifies dynamic characteristics of peripheral vagal HR control. In anesthetized Wistar-Kyoto rats (n = 7), the right vagal nerve was sectioned and stimulated for ten min according to a binary white noise sequence with a switching interval of 500 ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 12, 2019 Category: Physiology Authors: Kawada T, Yamamoto H, Uemura K, Hayama Y, Nishikawa T, Sugimachi M Tags: Am J Physiol Heart Circ Physiol Source Type: research

The potential role of Neddylation in pre- and postnatal cardiac remodeling.
PMID: 31274350 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 5, 2019 Category: Physiology Authors: Sadayappan S, Gilbert R Tags: Am J Physiol Heart Circ Physiol Source Type: research

Exaggerated cardiovascular responses to muscle contraction and tendon stretch in UCD Type-2 Diabetes Mellitus rats.
Abstract Type 2 diabetes mellitus (T2DM) patients have exaggerated sympathetic activity and blood pressure responses to exercise. However, the underlying mechanisms for these responses, as well as how these responses change throughout disease progression, are not completely understood. For this study, we examined the effect of the progression of T2DM on the exercise pressor reflex, a critical neuro-cardiovascular mechanism that functions to increase sympathetic activity and blood pressure during exercise. We also aimed to examine the effect of T2DM on reflexive cardiovascular responses to static contraction, as we...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 5, 2019 Category: Physiology Authors: Grotle AK, Crawford CK, Huo Y, Ybarbo KM, Harrison ML, Graham JL, Stanhope KL, Havel PJ, Fadel PJ, Stone AJ Tags: Am J Physiol Heart Circ Physiol Source Type: research

Sex and age differences in the association between sympathetic outflow and central elastic artery wall thickness in humans.
Abstract Aging is characterized by increased wall thickness of the central elastic arteries (i.e., aorta and carotid arteries), although the mechanisms involved are unclear. Evidence suggests that age-related increases in muscle sympathetic nerve activity (MSNA) may be a contributing factor. However, studies in humans have been lacking. Therefore, we tested the hypothesis that age-related increases in MSNA would be independently associated with carotid artery intima-media thickness (IMT), but not in young women given the reduced influence of MSNA on the vasculature in this group. In 93 young and middle-age/older (...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 5, 2019 Category: Physiology Authors: Holwerda SW, Luehrs RE, DuBose LE, Majee R, Pierce GL Tags: Am J Physiol Heart Circ Physiol Source Type: research

Exacerbated effects of prorenin on hypothalamic magnocellular neuronal activity and vasopressin plasma levels during salt-sensitive hypertension.
EXACERBATED EFFECTS OF PRORENIN ON HYPOTHALAMIC MAGNOCELLULAR NEURONAL ACTIVITY AND VASOPRESSIN PLASMA LEVELS DURING SALT-SENSITIVE HYPERTENSION. Am J Physiol Heart Circ Physiol. 2019 Jul 05;: Authors: Pitra S, Worker CJ, Feng Earley Y, Stern JE Abstract Accumulating evidence supports that the brain renin-angiotensin system (RAS) including prorenin (PR) and its receptor (PRR), two newly discovered RAS players, contribute to sympathoexcitation in salt-sensitive hypertension. Still, whether PR also contributed to elevated circulating levels of neurohormones such as vasopressin (VP) during salt-sensitive...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 5, 2019 Category: Physiology Authors: Pitra S, Worker CJ, Feng Earley Y, Stern JE Tags: Am J Physiol Heart Circ Physiol Source Type: research

Cardioprotection by the mitochondrial unfolded protein response (UPRmt) requires ATF5.
Abstract The mitochondrial unfolded protein response (UPRmt) is a cytoprotective signaling pathway triggered by mitochondrial dysfunction. UPRmt activation up-regulates chaperones, proteases, antioxidants, and glycolysis at the gene level to restore proteostasis and cell energetics. Activating transcription factor 5 (ATF5) is a proposed mediator of the mammalian UPRmt. Herein, we hypothesized pharmacologic UPRmt activation may protect against cardiac ischemia-reperfusion (IR) injury, in an ATF5-dependent manner. Accordingly, in-vivo administration of the UPRmt inducers oligomycin or doxycycline 6 hours prior to ex...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 5, 2019 Category: Physiology Authors: Wang YT, Lim Y, McCall MN, Huang KT, Haynes CM, Nehrke K, Brookes PS Tags: Am J Physiol Heart Circ Physiol Source Type: research

Evidence of Functional Ryanodine Receptors in Rat Mesenteric Collecting Lymphatic Vessels.
Abstract In the current study, the potential contributions of ryanodine receptors (RyR) to intrinsic pumping and responsiveness to substance P (SP) were investigated in isolated rat mesenteric collecting lymphatic vessels. Responses to SP were characterized in lymphatic vessels in the absence or presence of pretreatment with nifedipine to block L-type Ca2+ channels, caffeine to block normal release and uptake of Ca2+ from the sarcoplasmic reticulum (SR), ryanodine to block all RyR isoforms, or dantrolene to more selectively block RyR1 and RyR3. RyR expression and localization in lymphatics was also assessed by qPC...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 5, 2019 Category: Physiology Authors: Jo M, Trujillo AN, Yang Y, Breslin JW Tags: Am J Physiol Heart Circ Physiol Source Type: research

The Impact of Diet on the Persistence of Early Vascular Remodeling and Stiffening Induced by Intrauterine Growth Restriction and a Maternal High-fat Diet.
Abstract Intrauterine growth restriction (IUGR) and maternal high-fat diet (HFD) independently predispose offspring to hypertension. In a rat model, IUGR more so than maternal HFD increases arterial stiffness with vascular remodeling as early as post-natal day (PND) 21. The trajectory of such early vascular changes remains unknown. We hypothesized that IUGR would increase blood pressure (BP), arterial stiffness, and markers of ongoing detrimental vascular remodeling in adult rats exposed to a maternal HFD regardless of weaning diet. Adult female rats were fed either a regular diet (RD) or an HFD prior to mating th...
Source: American Journal of Physiology. Heart and Circulatory Physiology - June 21, 2019 Category: Physiology Authors: Miller TA, Dodson RB, Mankouski A, Powers KN, Yang Y, Yu B, Zinkhan EK Tags: Am J Physiol Heart Circ Physiol Source Type: research