Validation of diagnostic criteria and histopathological characterization of cardiac rupture in the mouse model of non-reperfused myocardial infarction.
In conclusion, the reliability of autopsy in documentation of rupture in infarcted mice is dependent on the specific criteria used. Macrophage-driven inflammation and reduced activation of collagen-secreting reparative myofibroblasts may be involved in the pathogenesis of post-MI cardiac rupture. PMID: 32886000 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 4, 2020 Category: Physiology Authors: Hanna A, Shinde AV, Frangogiannis NG Tags: Am J Physiol Heart Circ Physiol Source Type: research

Exercise heat acclimation has minimal effects on left ventricular volumes, function and systemic hemodynamics in euhydrated and dehydrated trained humans.
rd JD Abstract Heat acclimation (HA) may improve the regulation of cardiac output (Q̇) through increased blood volume (BV) and left ventricular (LV) diastolic filling, and attenuate reductions in Q̇ during exercise-induced dehydration; however, these hypotheses have never been directly tested. Before and following 10-days exercise HA, eight males completed two trials of submaximal exercise in 33°C and 50% relative humidity while maintaining pre-exercise euhydrated body mass (EUH; -0.6±0.4%) or becoming progressively dehydrated (DEH; -3.6±0.7%). Rectal (Tre) and skin (Tsk) temperatures, heart ra...
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 4, 2020 Category: Physiology Authors: Travers G, González-Alonso J, Riding NR, Nichols D, Shaw A, Periard JD Tags: Am J Physiol Heart Circ Physiol Source Type: research

COVID-19 and hypertension - is the HSP60 culprit for the severe course and worse outcome?
Abstract The 60 kDa heat shock protein (HSP60) is a chaperone essential for mitochondrial proteostasis ensuring thus sufficient aerobic energy production. In pathological conditions, HSP60 can be translocated from the mitochondria and excreted from the cell. In turn, the extracellular HSP60 has a strong ability to trigger and enhance inflammatory response with marked pro-inflammatory cytokine induction, which is mainly mediated by toll-like receptors binding. Previous studies have found increased circulating levels of HSP60 in hypertensive patients, as well as enhanced HSP60 expression and membrane translocation i...
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 4, 2020 Category: Physiology Authors: Jakovac H Tags: Am J Physiol Heart Circ Physiol Source Type: research

Rhythm Dynamics of the Aging Heart: an Experimental Study Using Conscious, Restrained Mice.
Abstract Heart rate variability (HRV) is a measure of variation in time interval between heartbeats and reflects the influence of autonomic nervous system and circulating/locally released factors on sinoatrial node discharge. Here, we tested whether electrocardiograms (ECGs) obtained in conscious, restrained mice, a condition that affects sympathovagal balance, reveal alterations of heart rhythm dynamics with aging. Moreover, based on emergence of sodium channels as modulators of pacemaker activity, we addressed consequences of altered sodium channels on heart rhythm. C57Bl/6 mice and mice with enhanced late sodiu...
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 4, 2020 Category: Physiology Authors: Comelli M, Meo M, Cervantes DO, Pizzo E, Plosker A, Mohler PJ, Hund TJ, Jacobson JT, Meste O, Rota M Tags: Am J Physiol Heart Circ Physiol Source Type: research

Prediction of hemodynamics after atrial septal defect closure using a framework of circulatory equilibrium in dogs.
The objective of this study was to develope a novel framework for quantitative prediction of hemodynamics after ASD closure. The generalized circulatory equilibrium comprises right and left cardiac output (CO) curves, and pulmonary and systemic venous return surfaces. We incorporated ASD into the framework of circulatory equilibrium by representing ASD shunt flow (QASD) by the difference between pulmonary flow (QP) and systemic flow (QS). To examine the accuracy of prediction, we created ASD in six dogs. Four weeks after ASD creation, we measured left atrial pressure (PLA), right atrial pressure (PRA), QP and Qs before and...
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 4, 2020 Category: Physiology Authors: Uike K, Saku K, Nishikawa T, Yamamura K, Nagata H, Muraoka M, Ohga S, Tsutsui H, Sunagawa K Tags: Am J Physiol Heart Circ Physiol Source Type: research

Endothelial function and shear stress in hypobaric hypoxia: time course and impact of plasma volume expansion in men.
We examined the temporal changes in blood viscosity, shear stress and endothelial function and the impact of plasma volume expansion (PVX) during exposure to hypobaric hypoxia while controlling for external factors. Eleven healthy males (25±4 years; mean±SD) completed two four-day chamber visits (normoxia [NX] and hypobaric hypoxia [HH; equivalent altitude: 3500m]) in a cross-over design. Endothelial function was assessed via flow-mediated dilation in response to transient (reactive hyperemia; RH-FMD) and sustained (progressive handgrip exercise; SS-FMD) increases in shear stress prior to entering and after 1...
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 4, 2020 Category: Physiology Authors: Tremblay JC, Ainslie PN, Turner REF, Gatterer H, Schlittler M, Woyke S, Regli IB, Strapazzon G, Rauch S, Siebenmann C Tags: Am J Physiol Heart Circ Physiol Source Type: research

CpG-postconditioning after reperfused myocardial infarction is associated with modulated inflammation, less apoptosis and better left ventricular function.
CONCLUSION: Our study suggests a cardioprotective mechanism of CpG-postconditioning, involving TLR-driven modulation of inflammation. This is followed by attenuated remodeling and preserved LV-function. PMID: 32857588 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 28, 2020 Category: Physiology Authors: Duerr GD, Wu S, Schneider ML, Marggraf V, Weisheit CK, Velten M, Verfuerth L, Frede S, Boehm O, Treede H, Dewald O, Baumgarten G, Kim SC Tags: Am J Physiol Heart Circ Physiol Source Type: research

Mitochondrial Calcium Uniporter Complex Activation Protects Against Calcium Alternans in Atrial Myocytes.
Abstract Cardiac alternans, defined as beat-to-beat alternations in action potential duration, cytosolic Ca transient (CaT) amplitude and cardiac contraction, is associated with atrial fibrillation (AF) and sudden cardiac death. At the cellular level, cardiac alternans is linked to abnormal intracellular calcium handling during excitation-contraction coupling. We investigated how pharmacological activation or inhibition of cytosolic Ca sequestration via mitochondrial Ca uptake and mitochondrial Ca retention affects the occurrence of pacing-induced CaT alternans in isolated rabbit atrial myocytes.Cytosolic CaTs wer...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 28, 2020 Category: Physiology Authors: Oropeza-Almazan Y, Blatter LA Tags: Am J Physiol Heart Circ Physiol Source Type: research

Enhanced KCl-mediated contractility and Ca2+ sensitization in porcine collateral-dependent coronary arteries persists after exercise training.
Abstract We have previously reported enhanced Ca2+ sensitivity of coronary arteries that are dependent upon collateral circulation for their blood supply. For the current study, we hypothesized that small collateral-dependent arteries would exhibit an enhanced KCl-mediated contractile response attributable to Ca2+ sensitization and increased Ca2+ channel current. Ameroid constrictors were surgically placed around the left circumflex (LCX) artery of female Yucatan miniature swine. Eight weeks post-operatively, pigs were randomized into sedentary or exercise-trained (treadmill run; 5 days/week; 14 weeks) groups. Sma...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 28, 2020 Category: Physiology Authors: Heaps CL, Bray JF, Parker JL Tags: Am J Physiol Heart Circ Physiol Source Type: research

Comprehensive MRI assessment of the cardiovascular responses to food ingestion in Fontan physiology.
In conclusion, alterations in vascular tone to counteract adverse hemodynamics and raised hepatic afterload may blunt vasoreactivity in the legs and the celiac axis in Fontan physiology. Further study is needed to determine whether blunted celiac or mesenteric vasoreactivity is linked to deteriorating hemodynamics and poor prognosis in Fontan patients. PMID: 32857602 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 28, 2020 Category: Physiology Authors: Hauser JA, Jones A, Pandya B, Taylor AM, Muthurangu V Tags: Am J Physiol Heart Circ Physiol Source Type: research

Sympathetic arterial baroreflex hysteresis in humans: different patterns during low and high pressure levels.
ar PJ Abstract Fluctuations in diastolic pressure modulates muscle sympathetic nerve activity (MSNA) through the arterial baroreflex. A higher sympathetic baroreflex sensitivity (sBRS) to pressure falls compared to rises has been reported, however, the underlying mechanisms are unclear. We assessed whether beat-to-beat falling and rising diastolic pressures operate on two distinct baroreflex response curves. Twenty-two men (32±8 years) underwent sequential bolus injections of nitroprusside and phenylephrine (modified Oxford test) with continuous recording of heart rate, blood pressure, and MSNA. The weighte...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 28, 2020 Category: Physiology Authors: Incognito AV, Samora M, Shepherd AD, Cartafina RA, Guimarães GMN, Daher M, Vianna LC, Millar PJ Tags: Am J Physiol Heart Circ Physiol Source Type: research

Four weeks of vitamin D supplementation improves nitric oxide-mediated microvascular function in college-aged African Americans.
Abstract Nitric oxide (NO)-mediated endothelial dysfunction, secondary to increased oxidative stress, presents in young African American (AA) compared to European American (EA) adults, and may be modulated by vitamin D status. We assessed cutaneous microvascular function in 18 young, healthy (21±2 yr; 9 M, 9 F) subjects before (pre: 8 AA, 10 EA) and 13 subjects after (post: 7 AA, 6 EA) four weeks of 2,000 IU/day oral vitamin D supplementation. Serum vitamin D concentrations [25(OH)D] were measured at each visit. Three intradermal microdialysis fibers placed in the ventral forearm were randomized for treatme...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 28, 2020 Category: Physiology Authors: Wolf ST, Jablonski NG, Ferguson SB, Alexander LM, Kenney WL Tags: Am J Physiol Heart Circ Physiol Source Type: research

Beyond oxygen transport: Active role of erythrocytes in the regulation of blood flow.
Abstract It was classically thought that the function of mammalian red blood cells (RBC) was limited to serving as a vehicle for oxygen, given the cell's abundance of cytosolic haemoglobin. Over the past decades, however, accumulating evidence indicates that RBC have the capacity to sense low oxygen tensions in hypoxic tissues, and subsequently release signalling molecules that influence the distribution of blood flow. The precise mechanisms that facilitate RBC modulation of blood flow are still being elucidated, although recent evidence indicates involvement of: i) adenosine triphosphate (ATP) - capable of bindin...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 28, 2020 Category: Physiology Authors: Richardson KJ, Kuck L, Simmonds MJ Tags: Am J Physiol Heart Circ Physiol Source Type: research

p38 δ genetic ablation protects female mice from anthracycline cardiotoxicity.
CONCLUSIONS: p38d plays a crucial role in promoting DOX-induced cardiotoxicity in female mice by inhibiting autophagy. Therefore, p38d targeting could be a potential cardioprotective strategy in anthracycline chemotherapy. PMID: 32822209 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 21, 2020 Category: Physiology Authors: George S, Kiss A, Obaid SN, Venegas A, Talapatra T, Wei C, Efimova T, Efimov IR Tags: Am J Physiol Heart Circ Physiol Source Type: research

The Ubiquitin Ligase WWP1 Contributes to Shifts in Matrix Proteolytic Profiles and a Myocardial Ageing Phenotype with Diastolic Heart Failure.
Abstract AIMS: Ubiquitylation is a key event that regulates protein turnover, and induction of the ubiquitin ligase E3 WWP1 has been associated with age. Left ventricular hypertrophy (LVH) commonly occurs as a function of age and can cause heart failure with a preserved ejection fraction (EF; HFpEF). We hypothesized that overexpression of WWP1 in the heart would cause LVH as well as functional and structural changes consistent with the aging HFpEF phenotype. METHODS AND RESULTS: Global WWP1 O/E was achieved in mice (n=11) and echocardiography (40 MHz) performed to measure LV mass, EF, Doppler velocities (earl...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 21, 2020 Category: Physiology Authors: Matesic LE, Freeburg LA, Snyder L, Duncan LM, Moore A, Perreault PE, Zellars KN, Goldsmith EC, Spinale FG Tags: Am J Physiol Heart Circ Physiol Source Type: research

More Purinergic Receptors Deserve Attention as Therapeutic Targets for the Treatment of Cardiovascular Disease.
Abstract Cardiovascular disease is a major cause of morbidity and mortality worldwide. Innovative new treatment options for this cardiovascular pandemic are urgently needed. Activation of purinergic receptors (PRs) is critically involved in the development and progression of cardiovascular disease including atherosclerosis, ischemic heart disease, hypertension and diabetes. PRs have been targeted for the treatment of several cardiovascular diseases in a clinical setting. The P2Y12R antagonists such as clopidogrel, ticagrelor and others are the most successful class of purinergic drugs targeting platelets for the t...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 21, 2020 Category: Physiology Authors: Wernly B, Zhou Z Tags: Am J Physiol Heart Circ Physiol Source Type: research

Biomechanics of Diastolic Dysfunction: a 1D Computational Modelling Approach.
In this study, we have developed a computational model of DD by leveraging the power of an advanced one-dimensional (1D) arterial network coupled to a four-chambered 0D cardiac model. The two main pathologies investigated were linked to the active relaxation of the myocardium and the passive stiffness of the left ventricular wall. These pathologies were quantified through two parameters for the biphasic delay of active relaxation, which simulate the early and late phase relaxation delay, and one parameter for passive stiffness, which simulates the increased non-linear stiffness of the ventricular wall. A parameter sensitiv...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 21, 2020 Category: Physiology Authors: Kadry K, Pagoulatou SZ, Mercier Q, Rovas G, Bikia V, Müller H, Adamopoulos D, Stergiopulos N Tags: Am J Physiol Heart Circ Physiol Source Type: research

Cardiac function during heat stress: Impact of short-term passive heat acclimation.
Abstract A lower heart rate (HR) during heat exposure is a classic marker of heat acclimation (HA), although it remains unclear whether this adaptation occurs secondary to reduced thermal strain and/or improvements in cardiac function. We evaluated the hypothesis that short-term passive HA reduces HR and improves cardiac function during passive heating. Echocardiography was performed under thermoneutral and hyperthermic conditions in 10 healthy adults (9 males/1 female, 29 ± 6 years old), pre and post 7 days of controlled hyperthermia. HR (P=0.61), stroke volume (P=0.99) and cardiac output (P=0.99) were sim...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 21, 2020 Category: Physiology Authors: Trachsel LD, Barry H, Gravel H, Behzadi P, Henri C, Gagnon D Tags: Am J Physiol Heart Circ Physiol Source Type: research

Atherogenic diet diminished endothelial glycocalyx contributes to impaired vasomotor properties in rat.
Abstract Hypercholesterolemia and atherosclerosis caused vasomotor properties dysfunction may be involved in many clinic manifestations of atherosclerosis, including angina, acute myocardial infarction, and sudden cardiac death. However, its underlying mechanism is not clear. The endothelial glycocalyx is a protective surface layer on the endothelial cells, serving as a molecular sieve, cell adhesion modulator, and mechanosensor for blood flow. In the present study, we demonstrated by confocal microscopy that the dimension of the endothelial glycocalyx reduced significantly in both the common carotid artery (2.89&...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 21, 2020 Category: Physiology Authors: Kang H, Sun A, Wu Q, Yang J, Zhang W, Qu Y, Gao M, Deng X Tags: Am J Physiol Heart Circ Physiol Source Type: research

Greater α1-adrenergic mediated vasoconstriction in contracting skeletal muscle of patients with type 2 diabetes.
Greater α1-adrenergic mediated vasoconstriction in contracting skeletal muscle of patients with type 2 diabetes. Am J Physiol Heart Circ Physiol. 2020 Aug 21;: Authors: Bock JM, Hughes W, Ueda K, Feider AJ, Hanada S, Kruse NT, Iwamoto E, Casey DP Abstract Patients with type 2 diabetes mellitus (T2DM) exhibit diminished exercise capacity likely attributable to reduced skeletal muscle blood flow (i.e., exercise hyperemia). A potential underlying mechanism of the impaired hyperemic response to exercise could be inadequate blunting of sympathetic-mediated vasoconstriction (i.e., poor functional symp...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 21, 2020 Category: Physiology Authors: Bock JM, Hughes W, Ueda K, Feider AJ, Hanada S, Kruse NT, Iwamoto E, Casey DP Tags: Am J Physiol Heart Circ Physiol Source Type: research

Hormetic modulation of angiogenic factors by exercise-induced mechanical and metabolic stress in human skeletal muscle.
This study used an integrative experimental model in humans to investigate whether muscle angiogenic factors are differentially modulated by exercise stimuli eliciting different degrees of mechanical and metabolic stress. In a randomized crossover design, twelve men performed two low‑volume high-intensity exercise regimens, including short sprint intervals (SSI) or long sprint intervals (LSI) inducing pronounced mechanical/metabolic stress, and a high‑volume moderate‑intensity continuous exercise protocol (MIC) inducing mild but prolonged mechanical/metabolic stress. Gene and protein expression of angioregulatory fac...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 21, 2020 Category: Physiology Authors: Fiorenza M, Gliemann L, Brandt N, Bangsbo J Tags: Am J Physiol Heart Circ Physiol Source Type: research

Transcriptional regulation by methyltransferases and their role in the heart: highlighting novel emerging functionality.
Abstract Methyltransferases are a superfamily of enzymes that transfer methyl groups to proteins, nucleic acids and small molecules. Traditionally, these enzymes have been shown to carry out a specific modification (mono-, di- or trimethylation) on a single, or limited number of, amino acid(s). The largest subgroup of this family, protein methyltransferases, target arginine and lysine side chains of histone molecules to regulate gene expression. While there is a large number of functional studies, which have been performed on individual methyltransferases describing their methylation targets and effects on biologi...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 21, 2020 Category: Physiology Authors: Szulik MW, Davis K, Bakhtina A, Azarcon P, Bia R, Horiuchi E, Franklin S Tags: Am J Physiol Heart Circ Physiol Source Type: research

Functional Coculture of Sympathetic Neurons and Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells.
Abstract Sympathetic neurons (SNs) capable of modulating the heart rate of murine cardiomyocytes (CMs) can be differentiated from human stem cells. The electrophysiological properties of human stem cell derived SNs remain largely uncharacterised, and human neurocardiac cocultures remain to be established. Here we have adapted previously published differentiation and coculture protocols to develop feeder-free SNs using human induced pluripotent stem cells (hiPSCs). hiPSC-SNs were characterized in mono- and coculture with hiPSC-CMs, using antibody labelling, enzyme-linked immunosorbent assay, and whole-cell patch cl...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 21, 2020 Category: Physiology Authors: Winbo A, Ramanan S, Eugster E, Jovinge S, Skinner JR, Montgomery JM Tags: Am J Physiol Heart Circ Physiol Source Type: research

Mechanism Underlying Increased Cardiac Extracellular Matrix Deposition in Perinatal Nicotine Exposed Offspring.
Abstract Although increased predisposition to cardiac fibrosis and cardiac dysfunction has been demonstrated in the perinatally nicotine exposed heart, the underlying mechanisms remain unclear. Using a well-established rat model and cultured primary neonatal rat cardiac fibroblasts, the effect of perinatal nicotine exposure on offspring heart extracellular matrix deposition and the likely underlying mechanisms were investigated. Perinatal nicotine exposure resulted in increased collagen type I (COL1A1) and III (COL3A1) deposition along with a decrease in miR-29 family and an increase in long non-coding RNA myocard...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 14, 2020 Category: Physiology Authors: Chuang TD, Ansari A, Yu C, Sakurai R, Harb A, Liu J, Khorram O, Rehan VK Tags: Am J Physiol Heart Circ Physiol Source Type: research

Diet-induced obese mouse hearts tolerate an acute high fatty acid exposure that also increases ischemic tolerance.
Abstract An ischemic insult is accompanied by an acute increase in circulating fatty acid (FA), which can induce adverse changes related to cardiac metabolism/energetics. Although chronic hyperlipidemia contributes to the pathogenesis of obesity/diabetes-related cardiomyopathy, it unclear how these hearts are affected by an acute high FA-load. We hypothesize that adaptation to chronic FA exposure enhances the obese hearts' ability to handle an acute high FA-load. Diet-induced obese (DIO) and age-matched control (CON) mouse hearts were perfused in the presence of low or high FA-load (0.4 and 1.8 mM). Left ventricul...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 14, 2020 Category: Physiology Authors: Boardman NT, Pedersen TM, Rossvoll L, Hafstad AD, Aasum E Tags: Am J Physiol Heart Circ Physiol Source Type: research

Injury-specific Inflammation Leads to Organ-specific Fibrosis.
;s LE PMID: 32795178 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 14, 2020 Category: Physiology Authors: Nazan Cakir S, de Castro Brás LE Tags: Am J Physiol Heart Circ Physiol Source Type: research

An integrated approach to simulating the vulnerable atherosclerotic plaque.
Abstract Analyses of individual atherosclerotic plaques are mostly descriptive, relying - for example - on histological classification by spectral analysis of ultrasound waves or staining and observing particular cellular components. Such passive methods have proved useful for characterizing the structure and vulnerability of plaques but have little quantitative predictive power. Our aim is to introduce and discuss a computational framework to provide insight to clinicians and help them visualize internal plaque dynamics. We use Partial Differential Equations (PDEs) with macrophages, necrotic cells, oxidized lipid...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 14, 2020 Category: Physiology Authors: Mohammad Mirzaei N, Weintraub WS, Fok PW Tags: Am J Physiol Heart Circ Physiol Source Type: research

Potential Mechanism of Left Ventricular Spherical Remodeling: Association of Mitral Valve Complex-Myocardium Longitudinal Tissue Remodeling Mismatch.
Abstract Since mitral valve (MV) complex (MVC) longitudinally bridges left ventricular (LV) base-end and its middle, insufficient MVC longitudinal tissue length (TL) elongation relative to whole LV myocardial longitudinal TL elongation could limit LV-base-longitudinal-TL elongation, leading to predominant LV-base-transverse-TL elongation, constituting LV spherical remodeling. In 30 patients with dilated cardiomyopathy (DCM), 30 with aortic regurgitation (AR), and 30 controls, LV sphericity, LV-apex- or base- transverse- and longitudinal-TL, MVC-longitudinal-TL and whole-LV-longitudinal-TL were measured by 3D echoc...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 14, 2020 Category: Physiology Authors: Nagata Y, Iwataki M, Nabeshima Y, Hei S, Onoue T, Hayashi A, Otani K, Tsuda Y, Araki M, Kim DH, Song JK, Hayashida A, Toki M, Yuasa T, Mizukami N, Nishimura Y, Levine R, Otsuji Y Tags: Am J Physiol Heart Circ Physiol Source Type: research

Endothelial Deficiency of Insulin-like Growth Factor -1 Receptor Reduces Endothelial Barrier Function and Promotes Atherosclerosis in Apoe-Deficient Mice.
Abstract Insulin-like growth factor-1 (IGF-1) decreases atherosclerosis in Apolipoprotein E (Apoe) -deficient mice when administered systemically. However, mechanisms for its atheroprotective effect are not fully understood. We generated endothelium-specific IGF-1 receptor (IGF1R) deficient mice on Apoe-deficient background to assess effects of IGF-1 on the endothelium in the context of hyperlipidemia-induced atherosclerosis. Endothelial deficiency of IGF1R promoted atherosclerotic burden, when animals were fed on high-fat diet for 12 weeks or normal chow for 12 months. Under normal chow feeding condition, the vas...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 14, 2020 Category: Physiology Authors: Higashi Y, Sukhanov S, Shai SY, Danchuk S, Snarski P, Li Z, Hou X, Hamblin MH, Woods TC, Wang M, Wang D, Yu H, Korthuis RJ, Yoshida T, Delafontaine P Tags: Am J Physiol Heart Circ Physiol Source Type: research

Early- and late-endothelial progenitor cells are negatively associated with the severity of vascular status in controlled hypertensive patients.
iar C Abstract Patients presenting classical cardiovascular risk factors within acceptable or average value ranges often develop cardiovascular disease, suggesting that other risk factors need to be considered. Considering that endothelial progenitor cells (EPC) contribute to endothelial repair, we investigated whether EPC might be such a factor. We compared the ability of peripheral blood EPC to attach to extracellular matrix proteins, and to grow and function in culture, between controlled-hypertensive patients exhibiting Framingham scores (FS)
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 14, 2020 Category: Physiology Authors: de Cavanagh EAM, Gonzalez SA, Inserra F, Forcada PJ, Castellaro CE, Chiabaut-Svane JA, Obregón S, Casarini MJ, Kempny P, Kotliar C Tags: Am J Physiol Heart Circ Physiol Source Type: research

Stimulus-specific functional remodeling of the left ventricle in endurance and resistance-trained men.
In conclusion, resistance-trained individuals better maintained SV during pressure loading, whereas endurance-trained individuals demonstrated greater EDV reserve during volume loading. These data provide novel evidence of training-specific LV functional remodeling. PMID: 32772543 [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, 2020 Category: Physiology Authors: Dawkins TG, Curry BA, Drane A, Lord RN, Richards C, Brown M, Pugh CJA, Lodge FM, Yousef Z, Stembridge M, Shave RE Tags: Am J Physiol Heart Circ Physiol Source Type: research

Synergy in the heart: RV systolic function plays a key role in optimizing LV performance during exercise.
Abstract The right ventricle (RV) is often overlooked in the evaluation of cardiac performance and treatment of left ventricular (LV) heart diseases. However, recent evidence suggests the RV may play an important role in maintaining systemic cardiac function and delivering stroke volume (SV). We used exercise cardiac magnetic resonance and biomechanical modeling to investigate the role of the RV in LV stroke volume regulation. We studied SV augmentation during exercise by pharmacologically inducing negative chronotropy (sHRi) in healthy volunteers and investigating training-induced SV augmentation in endurance ath...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 7, 2020 Category: Physiology Authors: Ruijsink B, Nieves Velasco-Forte M, Duong P, Asner L, Pushparajah K, Frigiola A, Nordsletten D, Razavi R Tags: Am J Physiol Heart Circ Physiol Source Type: research

Vascular Mechanisms and Molecular Targets in Hypertensive Pregnancy and Preeclampsia.
Abstract Preeclampsia is a major complication of pregnancy manifested as hypertension and often intrauterine growth restriction, but the underlying pathophysiological mechanisms are unclear. Predisposing genetic and environmental factors cause placental maladaptations leading to defective placentation, apoptosis of invasive cytotrophoblasts, inadequate expansive remodeling of the spiral arteries, reduced uteroplacental perfusion pressure and placental ischemia. Placental ischemia promotes the release of bioactive factors into the maternal circulation, causing an imbalance between anti-angiogenic soluble fms-like t...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 7, 2020 Category: Physiology Authors: Qu H, Khalil RA Tags: Am J Physiol Heart Circ Physiol Source Type: research

Enhanced dimethylarginine degradation improves coronary flow reserve and exercise tolerance in Duchenne muscular dystrophy carrier mice.
Abstract Duchenne muscular dystrophy (DMD) is an X-linked disease caused by null mutations in dystrophin and characterized by muscle degeneration. Cardiomyopathy is common and often prevalent at similar frequency in female DMD carriers irrespective of whether they manifest skeletal muscle disease. Impaired muscle nitric oxide (NO) production in DMD disrupts muscle blood flow regulation and exaggerates post-exercise fatigue. We show that circulating levels of endogenous methylated arginines including asymmetric dimethylarginine (ADMA), which act as NO synthase inhibitors, are elevated by acute necrotic muscle damag...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 7, 2020 Category: Physiology Authors: Garbincius JF, Merz LE, Cuttitta AJ, Bayne KV, Schrade S, Armstead EA, Converso-Baran KL, Whitesall SE, D'Alecy LG, Michele DE Tags: Am J Physiol Heart Circ Physiol Source Type: research

Metabolism of vascular smooth muscle cells in vascular diseases.
Abstract Vascular smooth muscle cells (VSMCs) are the fundamental component of the medial layer of arteries and are essential for arterial physiology and pathology. It is becoming increasingly clear that VSMCs can alter their metabolism to fulfill the bio-energetic and biosynthetic requirements. During vascular injury, VSMCs switch from a quiescent "contractile" phenotype to a highly migratory and proliferative "synthetic" phenotype. Recent studies find that the phenotype switching of VSMCs is driven by a metabolic switch. Metabolic pathways, including aerobic glycolysis, fatty acid oxidation, ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 7, 2020 Category: Physiology Authors: Shi J, Yang Y, Cheng A, Xu G, He F Tags: Am J Physiol Heart Circ Physiol Source Type: research

Myeloperoxidase Instigates Proinflammatory Responses in a Cecal Ligation and Puncture Rat Model of Sepsis.
Abstract Myeloperoxidase (MPO)-derived hypochlorous (HOCl) reacts with membrane plasmalogens to yield α-chlorofatty aldehydes such as 2-chlorofatty aldehyde (2-ClFALD) and its metabolite 2-chlorofatty acid (2-ClFA). Recent studies showed that 2-ClFALD and 2-ClFA serve as mediators of the inflammatory responses to sepsis by as yet unknown mechanisms. Since no scavenger for chlorinated lipids is available and based on the well-established role of the MPO/HOCl/chlorinated lipids axis in inflammatory responses, we hypothesized that treatment with MPO inhibitors (N-acetyl lysyltyrosylcysteine amide or 4-aminobenz...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 7, 2020 Category: Physiology Authors: Yu H, Liu Y, Wang M, Restrepo RJ, Wang D, Kalogeris TJ, Neumann WL, Ford DA, Korthuis RJ Tags: Am J Physiol Heart Circ Physiol Source Type: research

Diabetes and COVID-19 risk: a miRNA perspective.
Abstract COVID-19 and Diabetes Outcomes (CORONADO) trial revealed that 10.6% of diabetes mellitus patients hospitalized for coronavirus disease 2019 (COVID-19) and die within 7 days. Several studies from New York, Italy, and China confirm that diabetic patients are at a much high risk for mortality due to COVID-19. Besides respiratory illness, COVID-19 increases cardiac injury, and diabetic ketoacidosis. In the absence of specific guidelines for the prevention and treatment of COVID-19 for diabetic patients, they remain at higher risk and are more susceptible to COVID-19. Further, there is a scarcity of basic know...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 7, 2020 Category: Physiology Authors: Mishra PK, Tandon R, Byrareddy SN Tags: Am J Physiol Heart Circ Physiol Source Type: research

Letter to the editor: Sympathetically mediated increases in cardiac output, or peripheral vasoconstriction as primary regulator of BP during hyperinsulinemia?
PMID: 32748680 [PubMed - in process] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 1, 2020 Category: Physiology Authors: Fadel PJ, Young BE, Holwerda SW, Keller DM Tags: Am J Physiol Heart Circ Physiol Source Type: research

Reply to "Letter to the editor: Sympathetically mediated increases in cardiac output, or peripheral vasoconstriction as primary regulator of BP during hyperinsulinemia?"
Reply to "Letter to the editor: Sympathetically mediated increases in cardiac output, or peripheral vasoconstriction as primary regulator of BP during hyperinsulinemia?" Am J Physiol Heart Circ Physiol. 2020 Aug 01;319(2):H394-H395 Authors: Limberg JK, Padilla J PMID: 32748681 [PubMed - in process] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 1, 2020 Category: Physiology Authors: Limberg JK, Padilla J Tags: Am J Physiol Heart Circ Physiol Source Type: research

Corrigendum.
Authors: PMID: 32692955 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 22, 2020 Category: Physiology Tags: Am J Physiol Heart Circ Physiol Source Type: research

Cardiometabolic risk factors are associated with immune cell mitochondrial respiration in humans.
ns CR Abstract Modifiable cardiometabolic risk factors induce the release of pro-inflammatory cytokines and reactive oxygen species from circulating peripheral blood mononuclear cells (PBMCs) resulting in increased cardiovascular disease risk and compromised immune health. These changes may be driven by metabolic reprogramming of PBMCs resulting in impaired mitochondrial respiration; however, this has not been fully tested. We aimed to determine the independent associations between cardiometabolic risk factors, such as blood pressure, BMI, and plasma lipids with impaired mitochondrial respiration in PBMCs isolated...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 17, 2020 Category: Physiology Authors: DeConne TM, Muñoz ER, Sanjana F, Hobson JC, Martens CR Tags: Am J Physiol Heart Circ Physiol Source Type: research

Attenuating loss of cardiac conduction during no-flow ischemia through changes in perfusate sodium and calcium.
Abstract Myocardial ischemia leads to conduction slowing, cell-to-cell uncoupling, and arrhythmias. We previously demonstrated that varying perfusate sodium (Na+) and calcium (Ca2+) attenuates conduction slowing and arrhythmias during simulated ischemia with continuous perfusion. Cardioprotection was selectively associated with widening of the perinexus, a gap junction adjacent nanodomain important to ephaptic coupling. It is unknown whether perfusate composition affects the perinexus or ischemic conduction during non-simulated ischemia, when coronary flow is reduced or halted. We hypothesized that altering pre-is...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 17, 2020 Category: Physiology Authors: Hoeker GS, James CC, Tegge AN, Gourdie RG, Smyth JW, Poelzing S Tags: Am J Physiol Heart Circ Physiol Source Type: research

Quantification of Effects of Mean Blood Pressure and Left Ventricular Mass on Noninvasive Fast Fractional Flow Reserve.
This study aims to assess the influence of brachial mean blood pressure (MBP) and total coronary inflow on FFRB computation. Twenty-two patients underwent both CTCA and FFR measurements. Total coronary flow were computed from left ventricular mass (LVM) measured from CTCA. A total of 286 CFD simulations were run by varying MBP and LVM at 70, 80, 90, 100, 110, 120 and 130% of the measured values. FFRB increased with incrementally higher input values of MBP: 0.78 ± 0.12, 0.80 ± 0.11, 0.82 ± 0.10, 0.84 ± 0.09, 0.85 ± 0.08, 0.86 ± 0.08 and 0.87 ± 0.07, respectively. Conversely,...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 17, 2020 Category: Physiology Authors: Zhang JM, Chandola G, Tan R, Chai P, Teo LL, Low R, Allen JC, Huang W, Fam JM, Chin CY, Wong ASL, Low AF, Kassab GS, Chua TSJ, Tan SY, Lim ST, Zhong L Tags: Am J Physiol Heart Circ Physiol Source Type: research

Desmin is essential for the structure and function of the sinoatrial node; implications for increased arrhythmogenesis.
In conclusion, our results indicate that desmin elimination leads to structural and functional abnormalities of the (SANcl). These alterations may be enhanced by the sympathetic component of the cardiac autonomic nervous system, which is predominant in the desmin-deficient heart, thus leading to increased arrhythmogenesis. PMID: 32678709 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 17, 2020 Category: Physiology Authors: Mavroidis M, Athanasiadis NC, Rigas PS, Kostavasili I, Kloukina I, Te Rijdt WP, Kavantzas N, Chaniotis D, van Tintelen JP, Skaliora I, Davos CH Tags: Am J Physiol Heart Circ Physiol Source Type: research

The mechanism of osmotically-induced sealing of cardiac t-tubules.
In this study we use dextran trapping assay to demonstrate that in adult mouse cardiomyocytes t-tubular sealing can also be induced by hyperosmotic challenge, and that both hypo- and hyperosmotic sealing display a clear threshold behavior requiring ≈100 mOsm minimal stress. Importantly, during both hypo- and hyperosmotic challenges the sealing of t-tubules occurs only during the shrinking phase. Analysis of the time course of t-tubular remodeling following removal of hyposmotic stress shows that t-tubules become sealed essentially instantly, well before any significant reduction in cell size can be observed. Overall,...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 10, 2020 Category: Physiology Authors: Uchida K, Nikouee A, Moench I, Tamkus G, Elghoul Y, Lopatin AN Tags: Am J Physiol Heart Circ Physiol Source Type: research

Impacts of prolonged sitting with mild hypercapnia on vascular and autonomic function in healthy recreationally active adults.
Abstract Prolonged sitting, which is known to impair peripheral vascular function often occurs in spaces (e.g. offices) with mild hypercapnic atmospheres. However, the effects of prolonged sitting in hypercapnic conditions on vascular function are unknown. Therefore, the purpose of this study was to investigate the effects of prolonged sitting in mild hypercapnic conditions on vascular and autonomic function in humans. METHODS: 12 healthy young adults participated in two experimental visits which consisted of sitting for 2.5 hours in a control condition (PSIT) or a mild hypercapnic condition (HCAP, CO2=1,500 ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 10, 2020 Category: Physiology Authors: Headid RJ, Pekas EJ, Wooden TK, Son WM, Layec G, Shin J, Park SY Tags: Am J Physiol Heart Circ Physiol Source Type: research

The influence of barosensory vessel mechanics on the vascular sympathetic baroreflex: insights into ageing and blood pressure homeostasis.
In conclusion, in young men, aortic unloading mechanics may play a role in determining the vascular sympathetic baroreflex OP. In contrast, in middle-aged men, barosensory vessel unloading mechanics do not appear to determine the vascular sympathetic baroreflex OP, and therefore do not contribute to age-related arterial baroreflex resetting and increased resting MSNA. PMID: 32648822 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 10, 2020 Category: Physiology Authors: Lord RN, Wakeham DJ, Pugh CJA, Simpson LL, Talbot JS, Lodge FM, Curry BA, Dawkins TG, Shave RE, Moore JP Tags: Am J Physiol Heart Circ Physiol Source Type: research

In vivo [U-13C]-glucose labeling to assess heart metabolism in murine models of pressure and volume overload.
Abstract Alterations in the metabolism of substrates such as glucose are integrally linked to the structural and functional changes that occur in the remodeling heart. Assessment of such metabolic changes under in vivo conditions would provide important insights into this inter-relationship. We aimed to investigate glucose carbon metabolism in pressure-overload and volume-overload cardiac hypertrophy by using an in vivo [U-13C]-glucose labeling strategy to enable analyses of the metabolic fates of glucose carbons in the mouse heart. Therefore, [U-13C]-glucose was administered in anesthetized mice by tail vein infu...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 10, 2020 Category: Physiology Authors: Schnelle M, Chong M, Zoccarato A, Elkenani M, Sawyer GJ, Hasenfuss G, Ludwig C, Shah AM Tags: Am J Physiol Heart Circ Physiol Source Type: research

The Role of Endothelial Autocrine NRG1/ERBB4 Signaling in Cardiac Remodeling.
This study contributes to understanding the spatio-temporal heterogeneity of myocardial autocrine and paracrine responses following cardiac injury. PMID: 32618511 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 3, 2020 Category: Physiology Authors: Dugaucquier L, Feyen E, Mateiu L, Bruyns TAMJ, De Keulenaer GW, Segers VF Tags: Am J Physiol Heart Circ Physiol Source Type: research

Progesterone promotes endothelial nitric oxide synthase expression through enhancing nuclear progesterone receptor-SP1 formation.
Abstract 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. Then, the interaction between SP1 and PR-A/B were determined through co-IP assay (co-immunoprecipitation). The ChIP (chromatin immunoprecipitation) assay...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 3, 2020 Category: Physiology Authors: You Y, Tan W, Guo Y, Luo M, Shang FF, Xia Y, Luo S Tags: Am J Physiol Heart Circ Physiol Source Type: research