Cores of Reproducibility in Physiology: Assessing Author Compliance with Data Presentation Guidelines for Manuscript Figures.
Abstract The present study was undertaken to address the concern that author compliance with American Physiological Society (APS) journal Instructions to Authors for data presentation in manuscript figures is inadequate. Common instances of non-compliance are omitted molecular weight markers for immunoblots and bar graphs lacking individual data points. The American Journal of Physiology - Heart and Circulatory Physiology (AJP-Heart and Circ) editorial team designed a program to assess figure data presentation in submitted manuscripts. The intended outcome was to improve author compliance with APS data presentatio...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 20, 2020 Category: Physiology Authors: Hansell Keehan K, Gaffney MC, Zucker IH Tags: Am J Physiol Heart Circ Physiol Source Type: research

Guidelines for Animal Exercise and Training Protocols for Cardiovascular Studies.
Abstract Whole body exercise tolerance is the consummate example of integrative physiological function among the metabolic, neuromuscular, cardiovascular and respiratory systems. Depending on the animal selected the energetic demands and flux through the oxygen transport system can increase two orders of magnitude from rest to maximal exercise. Thus, animal models in health and disease present the scientist with flexible and powerful, and in some instances, purpose-built tools to explore the mechanistic bases for physiologic function and help unveil the causes for pathological or age-related exercise intolerance. ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 20, 2020 Category: Physiology Authors: Poole DC, Copp SW, Colburn TD, Craig JC, Allen D, Sturek M, O'Leary DS, Zucker IH, Musch TI Tags: Am J Physiol Heart Circ Physiol Source Type: research

Abnormal myocardial expression of SAP97 is associated with arrhythmogenic risk.
Conclusions DLG1 joins a growing list of genes encoding ion channel interacting proteins (ChIPs) identified as potential channelopathy-susceptibility genes because of their ability to regulate the trafficking, targeting, and modulation of ion channels that are critical for the generation and propagation of the cardiac electrical impulse. Dysfunction in these critical components of cardiac excitability can result potentially in fatal cardiac disease. PMID: 32196358 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 20, 2020 Category: Physiology Authors: Musa H, Marcou CA, Herron TJ, Makara M, Tester DJ, O'Connell R, Rosinski B, Guerrero-Serna G, Milstein ML, Monteiro Da Rocha A, Ye D, Crotti L, Nesterenko VV, Castelletti S, Torchio M, Kotta MC, Dagradi F, Antzelevitch C, Mohler PJ, Schwartz PJ, Ackerman Tags: Am J Physiol Heart Circ Physiol Source Type: research

Low molecular weight heparin promotes transcription and release of placental growth factor from endothelial cells.
CONCLUSIONS: LMWH exposure promotes the release of PlGF from endothelial cells through the upregulation of PlGF-1 mRNA expression. Stimulation of circulating PlGF levels by LMWH may be an important mechanism by which LMWH could reduce the risk of preeclampsia, or minimize disease severity. PMID: 32196359 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 20, 2020 Category: Physiology Authors: McLaughlin K, Nadeem L, Wat J, Baczyk D, Lye SJ, Kingdom J Tags: Am J Physiol Heart Circ Physiol Source Type: research

Tobacco and Electronic Cigarettes Adversely Impact ECG Indices of Ventricular Repolarization: Implication for Sudden Death Risk.
Abstract Tobacco cigarette(TC) smoking is associated with increased sudden death risk, perhaps through adverse effects on ventricular repolarization(VP). The effect of electronic-cigarettes(ECs) on VP is unknown. Objective To test the hypothesis that TCs and ECs have similar adverse effects on electrocardiogram(ECG) indices of VP, and these effects are attributable to nicotine. Methods ECG recordings were obtained in 37 TC-smokers, 43 EC-users, and 65 non-users. Primary outcomes, Tpeak-to-Tend(Tp-e), Tp-e/QT, and Tp-e/QTc, were measured in TC-smokers pre/post straw-control and smoking one TC, and in EC-users and n...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 20, 2020 Category: Physiology Authors: Ip M, Diamantakos E, Haptonstall K, Choroomi Y, Moheimani RS, Nguyen KH, Tran E, Gornbein J, Middlekauff HR Tags: Am J Physiol Heart Circ Physiol Source Type: research

Endothelial calreticulin deletion impairs endothelial function in aged mice.
Abstract Discrete calcium signals within the vascular endothelium decrease with age and contribute to impaired endothelial dependent vasodilation. Calreticulin (Calr), a multifunctional calcium binding protein and endoplasmic reticulum (ER) chaperone, can mediate calcium signals and vascular function within the endothelial cells (EC) of small resistance arteries. We found Calr protein expression significantly decreases with age in mesenteric arteries and examined the functional role of EC Calr in vasodilation and calcium mobilization in the context of aging. Third order mesenteric arteries from mice with or withou...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 20, 2020 Category: Physiology Authors: Biwer LA, Askew-Page HR, Hong K, Milstein J, Johnstone SR, Macal E, Good ME, Bagher P, Sonkusare S, Isakson BE Tags: Am J Physiol Heart Circ Physiol Source Type: research

Novel insights into cardiac regeneration based on differential fetal and adult ovine heart transcriptomic analysis.
, Ghiringhelli PD Abstract The adult mammalian cardiomyocyte has a very limited capacity to re-enter the cell cycle and advance into mitosis. Therefore, diseases characterized by lost contractile tissue usually evolve into myocardial remodeling and heart failure. Analyzing the cardiac transcriptome at different developmental stages in a large mammal closer to the human than laboratory rodents may serve to disclose positive and negative cardiomyocyte cell cycle regulators potentially targetable to induce cardiac regeneration in the clinical setting. We thus aimed at characterizing the transcriptomic profiles of the...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 13, 2020 Category: Physiology Authors: Locatelli P, Belaich MN, López AE, Olea FD, Uranga Vega M, Giménez CS, Simonin A, Bauzá MDR, Castillo MG, Cuniberti LA, Crottogini A, Cerrudo CS, Ghiringhelli PD Tags: Am J Physiol Heart Circ Physiol Source Type: research

Tumor Necrosis Factor-alpha impairs cerebral blood flow in pregnant rats: Role of vascular beta-Epithelial Na+ Channel.
Abstract Preeclampsia is a pregnancy-related disorder characterized by hypertension, vascular dysfunction and an increase in circulating inflammatory factors including the cytokine, tumor necrosis factor-alpha (TNF-α). Studies have shown that placental ischemia is associated with 1) increased circulating TNF-α, 2) attenuated pressure-induced cerebral vascular tone and 3) suppression of beta-Epithelial Na+ Channel (βENaC) protein in cerebral vessels. βENaC is an essential signaling element in transduction of pressure-induced (aka "myogenic") constriction, a critical mechanism of bloo...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 13, 2020 Category: Physiology Authors: Duncan J, Younes ST, Hildebrandt E, Ryan MJ, Granger JP, Drummond HA Tags: Am J Physiol Heart Circ Physiol Source Type: research

The contribution of chymase-dependent formation of AngII to cardiac dysfunction in metabolic syndrome of young rats: roles of fructose and EETs.
In conclusions, HFD-driven adverse chymase/AngII/AT1R/Nox/superoxide signaling in young rats was prevented by inhibition of sEH via at least in part, an EET-mediated stabilization of mast cells, highlighting chymase and sEH as therapeutic targets during treatment of MetS. PMID: 32167781 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 13, 2020 Category: Physiology Authors: Froogh G, Kandhi S, Duvvi R, Le Y, Weng Z, Alruwaili N, Ashe JO, Sun D, Huang A Tags: Am J Physiol Heart Circ Physiol Source Type: research

Flow Profile Characteristics in Fontan Circulation are Associated with the Single Ventricle Dilation and Function: Principal Component Analysis Study.
MV Abstract The Fontan circulation is characterized as a non-pulsatile flow propagation without a pressure generating ventricle. However, flow through the Fontan circulation still exhibits oscillatory waves as a result of pressure changes generated by the systemic single ventricle. Identification of discrete flow patterns through the Fontan circuit may be important to understand single ventricle performance. 97 patients with Fontan circulation underwent phase-contrast MRI of the right pulmonary artery yielding subject specific flow wave-forms. Principal component analysis was performed on pre-processed flow-wavef...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 13, 2020 Category: Physiology Authors: Schäfer M, Frank BS, Humphries SM, Hunter KS, Carmody KL, Jacobsen R, Mitchell MB, Jaggers J, Stone ML, Morgan GJ, Barker AJ, Browne L, Ivy DD, Younoszai A, Di Maria MV Tags: Am J Physiol Heart Circ Physiol Source Type: research

Phosphoinositide 3-Kinase Therapy in Diabetic Cardiomyopathy: Unravelling an Enigma.
PMID: 32167783 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 13, 2020 Category: Physiology Authors: Bi Y, Zhang Y, Ren J Tags: Am J Physiol Heart Circ Physiol Source Type: research

PKCdelta causes sepsis-induced cardiomyopathy by inducing mitochondrial dysfunction.
Abstract Sepsis-induced cardiomyopathy (SIC) is associated with increased patient mortality. At present, there are no specific therapies for SIC. Previous studies have reported increased ROS and mitochondrial dysfunction during SIC. However, a unifying mechanism remains to be defined. We hypothesized that PKCdelta is required for abnormal calcium handling and cardiac mitochondrial dysfunction during sepsis, and that genetic deletion of PKCdelta would be protective. Polymicrobial sepsis induced by cecal ligation and puncture (CLP) surgery decreased the ejection fraction of WT mice but not PKCdelta KO mice. Similarl...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 6, 2020 Category: Physiology Authors: Joseph LC, Reyes MV, Lakkadi KR, Gowen BH, Hasko G, Drosatos K, Morrow JP Tags: Am J Physiol Heart Circ Physiol Source Type: research

Normative data and the influence of age and gender on microcirculatory function in a middle-aged cohort: Results from the SCAPIS study.
The objective of this study was to assess normative values for comprehensive forearm skin microcirculatory function: oxygen saturation, tissue fraction of red blood cells (RBCs) and speed resolved perfusion. Furthermore, to examine the influence of age and gender on microcirculatory function. Measurements were performed using a non-invasive probe-based system, including diffuse reflectance spectroscopy and laser Doppler flowmetry, yielding output data in absolute units. The study was conducted within the Swedish CArdioPulmonary BioImage Study (SCAPIS) and included 1765 men and women aged 50-65 years from the Linköping...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 6, 2020 Category: Physiology Authors: Jonasson H, Bergstrand S, Fredriksson I, Larsson M, Östgren CJ, Strömberg T Tags: Am J Physiol Heart Circ Physiol Source Type: research

The Deleterious Role of the Prostaglandin E2 EP3 Receptor in Angiotensin II Hypertension.
In conclusion, activation or overexpression of EP3 exacerbates end organ damage in Ang II HTN. In contrast, antagonism of the EP3 receptor is beneficial and reduces cardiac dysfunction, inflammation, and HTN. PMID: 32142358 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 6, 2020 Category: Physiology Authors: Bryson TD, Pandrangi TS, Khan SZ, Xu J, Pavlov TS, Ortiz PA, Peterson EL, Harding P Tags: Am J Physiol Heart Circ Physiol Source Type: research

Enhanced Cardiac Phosphoinositide 3-Kinase (p110 α) using Gene Therapy Attenuates Cardiac Remodeling in Type 2 Diabetic Mice.
Enhanced Cardiac Phosphoinositide 3-Kinase (p110α) using Gene Therapy Attenuates Cardiac Remodeling in Type 2 Diabetic Mice. Am J Physiol Heart Circ Physiol. 2020 Mar 06;: Authors: Prakoso D, De Blasio MJ, Tate M, Kiriazis H, Donner DG, Qian H, Nash D, Deo M, Weeks KL, Parry LJ, Gregorevic P, McMullen JR, Ritchie RH Abstract Diabetic cardiomyopathy is a distinct form of heart disease that represents a major cause of death and disability in diabetic patients, particularly the more prevalent type-2 diabetic population. In the current study, we investigated administration of recombinant adeno-assoc...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 6, 2020 Category: Physiology Authors: Prakoso D, De Blasio MJ, Tate M, Kiriazis H, Donner DG, Qian H, Nash D, Deo M, Weeks KL, Parry LJ, Gregorevic P, McMullen JR, Ritchie RH Tags: Am J Physiol Heart Circ Physiol Source Type: research

Arterial baroreflex regulation of muscle sympathetic single unit activity in men: influence of resting blood pressure.
na LC Abstract The arterial baroreflex has dominant control over multi-unit muscle sympathetic nerve activity (MSNA) burst occurrence but whether this extends to all single units or influenced by resting blood pressure status is unclear. In 22 men (32±8 years), we assessed 68 MSNA single units during sequential bolus injections of nitroprusside and phenylephrine (modified Oxford). Sympathetic baroreflex sensitivity (sBRS) was quantified as the weighted negative linear regression slope between diastolic blood pressure (DBP) and single unit spike firing probability and multiple spike firing. Strong negative l...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 6, 2020 Category: Physiology Authors: Incognito AV, Samora M, Shepherd AD, Cartafina RA, Guimarães GMN, Daher M, Millar PJ, Vianna LC Tags: Am J Physiol Heart Circ Physiol Source Type: research

Overview of Mathematical Modeling of Myocardial Blood Flow Regulation.
Abstract The oxygen consumption by the heart and its extraction from the coronary arterial blood are the highest among all organs. Any increase in oxygen demand due to a change in the heart metabolic activity requires an increase in coronary blood flow. This functional requirement of adjustment of coronary blood flow is mediated by coronary flow regulation to meet the oxygen demand without any discomfort, even under strenuous exercise conditions. The goal of this article is to provide an overview of the theoretical and computational models of coronary flow regulation, and to reveal insights into the functioning of...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 6, 2020 Category: Physiology Authors: Namani R, Lanir Y, Lee LC, Kassab GS Tags: Am J Physiol Heart Circ Physiol Source Type: research

Neural Control of Blood Pressure is Altered Following Isolated Leg Heating in Aged Humans.
Abstract There is a sustained reduction in arterial blood pressure that occurs in aged adults following exposure to acute leg heating. We tested the hypothesis that acute leg heating would decrease arterial blood pressure in aged adults secondary to sympathoinhibition. Thirteen young and 10 aged adults were exposed to 45 min of leg heating. Muscle sympathetic nerve activity (radial nerve) was measured before leg heating (Pre-heat) and 30 min after (Recovery), and is expressed as burst frequency. Neurovascular transduction was examined by assessing the slope of the relation between muscle sympathetic nerve activity...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 6, 2020 Category: Physiology Authors: Engelland RE, Hemingway HW, Tomasco OG, Olivencia-Yurvati AH, Romero SA Tags: Am J Physiol Heart Circ Physiol Source Type: research

Pulmonary hemodynamics and wave reflections in adults with atrial septal defects.
PULMONARY HEMODYNAMICS AND WAVE REFLECTIONS IN ADULTS WITH ATRIAL SEPTAL DEFECTS. Am J Physiol Heart Circ Physiol. 2020 Mar 06;: Authors: Ting CT, Chen JW, Chang MS, Yin FCP Abstract Using high-fidelity micromanometers and flow velocity sensors at right heart catheterization, we compared pulmonary hemodynamics and wave reflections in age-matched normal adults and those with atrial septal defects, separated into three subgroups based on levels of mean pulmonary artery pressure: low ( 26 mmHg). We made baseline measurements in all groups and after intravenous sodium nitroprusside in the subgroups. All t...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 6, 2020 Category: Physiology Authors: Ting CT, Chen JW, Chang MS, Yin FCP Tags: Am J Physiol Heart Circ Physiol Source Type: research

A Murine Model of Increased Coronary Sinus Pressure Induces Myocardial Edema with Cardiac Lymphatic Dilation and Fibrosis.
CONCLUSIONS: A novel surgical model of myocardial edema without infarct was established in mice. Cardiac lymphatics compensated by exhibiting both an acute dilatory and chronic growth response, that temporally differs between sexes. Transient myocardial edema was sufficient to induce a robust epicardial fibrotic and inflammatory response, again with distinct sex differences, which underscores the sex-dependent differences that exist in cardiac vascular physiology. PMID: 32142379 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 6, 2020 Category: Physiology Authors: Nielsen NR, Rangarajan KV, Mao L, Rockman HA, Caron KM Tags: Am J Physiol Heart Circ Physiol Source Type: research

Alternative diastolic function models of ventricular longitudinal filling velocity are mathematically identical.
ALTERNATIVE DIASTOLIC FUNCTION MODELS OF VENTRICULAR LONGITUDINAL FILLING VELOCITY ARE MATHEMATICALLY IDENTICAL. Am J Physiol Heart Circ Physiol. 2020 Mar 06;: Authors: Bhagavan D, Padovano WM, Kovacs SJ Abstract Noninvasive imaging has established the spatiotemporal features of normal, in-vivo cardiac motion. Long-axis cardiac motion has become a focus of Diastolic Function (DF) characterization, especially the Tissue Doppler e'-wave, which occurs in early diastole when the LV is a mechanical suction pump (dP/dV
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 6, 2020 Category: Physiology Authors: Bhagavan D, Padovano WM, Kovacs SJ Tags: Am J Physiol Heart Circ Physiol Source Type: research

Influence of multi-parity on sympathetic nerve activity during normal pregnancy.
CONCLUSION: Our results may highlight a possible role of altered within-pregnancy sympathetic neural regulation in the observed relationship in women between parity and future cardiovascular disease risk. PMID: 32142381 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 6, 2020 Category: Physiology Authors: Badrov MB, Yoo JK, Steinback CD, Davenport MH, Fu Q Tags: Am J Physiol Heart Circ Physiol Source Type: research

Reply to "Letter to the Editor: Importance of B cells in response to placental ischemia".
Reply to "Letter to the Editor: Importance of B cells in response to placental ischemia". Am J Physiol Heart Circ Physiol. 2020 Mar 01;318(3):H726-H728 Authors: Regal JF, Laule CF, Root KM, Gilbert JS, Fleming SD PMID: 32141767 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 1, 2020 Category: Physiology Authors: Regal JF, Laule CF, Root KM, Gilbert JS, Fleming SD Tags: Am J Physiol Heart Circ Physiol Source Type: research

Corrigendum.
Authors: PMID: 32141768 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 1, 2020 Category: Physiology Tags: Am J Physiol Heart Circ Physiol Source Type: research

Letter to the Editor: Importance of B cells in response to placental ischemia.
PMID: 32141769 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 1, 2020 Category: Physiology Authors: LaMarca B Tags: Am J Physiol Heart Circ Physiol Source Type: research

Distinct hemodynamic responses to (Pyr)Apelin-13 in large animal models.
This study tested the hypothesis that (pyr)apelin-13 dose-dependently augments myocardial contractility and coronary blood flow, irrespective of changes in systemic hemodynamics. Acute effects of intravenous (pyr)apelin-13 administration (10 nM to 1,000 nM) on blood pressure, heart rate, left ventricular pressure and volume, and coronary parameters were measured in dogs and pigs. Administration of (pyr)apelin-13 did not influence blood pressure (P = 0.59), dP/dt-max (P = 0.26) or dP/dt-min (P = 0.85) in dogs. However, heart rate dose-dependently increased>70% (P
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 28, 2020 Category: Physiology Authors: Tune JD, Baker HE, Berwick ZC, Moberly S, Casalini ED, Noblet JN, Zhen E, Kowala MC, Christe ME, Goodwill AG Tags: Am J Physiol Heart Circ Physiol Source Type: research

Systemic and Regional Hemodynamic Response to Activation of the Exercise Pressor Reflex in Patients with Peripheral Artery Disease.
Abstract Patients with peripheral arterial disease (PAD) have an accentuated exercise pressor reflex (EPR) during exercise of the affected limb. The underlying hemodynamic changes responsible for this, and its effect on blood flow to the exercising extremity is unclear. We tested the hypothesis that the exaggerated EPR in PAD is mediated by an increase in total peripheral resistance (TPR), which augments redistribution of blood flow to the exercising limb. Eleven PAD patients and 11 age, and sex-matched subjects without PAD performed dynamic plantar flexion (PF) using the most symptomatic leg at progressive worklo...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 28, 2020 Category: Physiology Authors: Kim DJ, Kuroki MT, Cui J, Gao Z, Luck JC, Pai S, Miller AJ, Sinoway LI Tags: Am J Physiol Heart Circ Physiol Source Type: research

Spinal cord neural network interactions: implications for sympathetic control of the porcine heart.
CONCLUSION: Increased intra-segmental network coherence within the thoracic spinal cord contributes to myocardial ischemia-induced sympathoexcitation. PMID: 32108524 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 28, 2020 Category: Physiology Authors: Dale EA, Kipke J, Kubo Y, Sunshine MD, Castro PA, Ardell JL, Mahajan A Tags: Am J Physiol Heart Circ Physiol Source Type: research

Heart Failure in Single Right Ventricle Congenital Heart Disease: Physiologic and Molecular Considerations.
Abstract Due to remarkable surgical and medical advances over the past several decades, there are growing numbers of infants and children living with single ventricle congenital heart disease (SV), where there is only one functional cardiac pumping chamber. Nevertheless, cardiac dysfunction and ultimately heart failure is a common complication in the SV population and pharmacologic heart failure therapies have largely been ineffective in mitigating the need for heart transplantation. Given that there are several inherent risk factors for ventricular dysfunction in the setting of SV in addition to probable differen...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 28, 2020 Category: Physiology Authors: Garcia AM, Beatty JT, Nakano SJ Tags: Am J Physiol Heart Circ Physiol Source Type: research

Sulforaphane Prevents Right Ventricular Injury and Reduces Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.
Abstract Right ventricular (RV) dysfunction is the main determinant of mortality in patients with pulmonary arterial hypertension (PAH) and while inflammation is pathogenic in PAH there is limited information on the role of RV inflammation in PAH. Sulforaphane (SFN), a potent Nrf2 activator, has significant anti-inflammatory effects and facilitates cardiac protection in preclinical diabetic models. Therefore, we hypothesized SFN might play a comparable role in reducing RV and pulmonary inflammation and injury in a murine PAH model. We induced PAH using SU5416 and 10% hypoxia (SuHx) for 4 weeks in male mice randomi...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 28, 2020 Category: Physiology Authors: Kang Y, Zhang G, Huang EC, Huang J, Cai J, Cai L, Wang S, Keller BB Tags: Am J Physiol Heart Circ Physiol Source Type: research

HIV-related Cardiovascular Diseases: the Search for a Unifying Hypothesis.
Abstract Although the extensive roll-out of antiretroviral (ARV) therapy resulted in a longer life expectancy for people living with human immunodeficiency virus (PLHIV), such individuals display a relatively increased occurrence of cardiovascular diseases (CVD). This health challenge stimulated significant research interests in the field, leading to an improved understanding of both lifestyle-related risk factors and the underlying mechanisms of CVD onset in PLHIV. However, despite such progress the precise role of various risk factors and mechanisms underlying the development of HIV-mediated CVD still remain rel...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 21, 2020 Category: Physiology Authors: Dominick L, Midgley N, Swart LM, Sprake D, Deshpande G, Laher I, Joseph DE, Teer E, Essop MF Tags: Am J Physiol Heart Circ Physiol Source Type: research

Mavacamten rescues increased myofilament calcium sensitivity and dysregulation of Ca2+ flux caused by thin filament hypertrophic cardiomyopathy mutations.
Abstract Thin filament hypertrophic cardiomyopathy (HCM) mutations increase myofilament Ca2+- sensitivity and alter Ca2+ handling and buffering. The myosin inhibitor mavacamten reverses the increased contractility caused by HCM thick filament mutations, and we here test its effect on HCM thin filament mutations where the mode of action is not known. Mavacamten (250 nM) partially reversed the increased Ca2+ sensitivity caused by HCM mutations cTnT R92Q and cTnI R145G in in vitro ATPase assays. The effect of mavacamten was also analysed in cardiomyocyte models of cTnT R92Q and cTnI R145G containing cytoplasmic and m...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 21, 2020 Category: Physiology Authors: Sparrow AJ, Watkins H, Daniels MJ, Redwood C, Robinson P Tags: Am J Physiol Heart Circ Physiol Source Type: research

Estrogen and Calcium Handing Proteins: New Discoveries and Mechanisms in Cardiovascular Diseases.
Abstract Estrogen deficiency is considered to be an important factor leading to cardiovascular diseases (CVDs). Indeed, the prevalence of CVDs in postmenopausal women exceeds that of premenopausal women and men of same age. Recent research findings provide evidence that estrogen plays a pivotal role in the regulation of calcium homeostasis, and hence fine-tunes normal cardiomyocytes contraction and relaxation processes. Disruption of calcium homeostasis is closely associated with the pathological mechanism of CVDs. Thus, this article maps out and summarizes the effects and mechanisms of estrogen on calcium handing...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 21, 2020 Category: Physiology Authors: Jiao L, Machuki JO, Wu Q, Shi M, Fu L, Adekunle AO, Tao X, Xu C, Hu X, Yin Z, Sun H Tags: Am J Physiol Heart Circ Physiol Source Type: research

The compendium of matrix metalloproteinase expression in the left ventricle of mice following myocardial infarction.
Abstract Matrix metalloproteinases (MMPs) are proteolytic enzymes that break down extracellular matrix (ECM) components and have shown to be highly active in the myocardial infarction (MI) landscape. In addition to breaking down ECM products, MMPs modulate cytokine signaling and mediate leukocyte cell physiology. MMP-2, -7, -8, -9, -12, -14, and -28 are well studied as effectors of cardiac remodeling after MI. While 13 MMPs have been evaluated in the MI setting, 13 MMPs have not been investigated during cardiac remodeling. Here we measure the remaining MMPs across the MI time continuum to provide the full catalogu...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 21, 2020 Category: Physiology Authors: Kaminski AR, Moore ET, Daseke Ii MJ, Valerio FM, Flynn ER, Lindsey ML Tags: Am J Physiol Heart Circ Physiol Source Type: research

Angiotensin-(1-7) reduces doxorubicin-induced cardiac dysfunction in male and female Sprague-Dawley rats through antioxidant mechanisms.
This study investigated whether adjunct Ang-(1-7) attenuates cardiotoxicity resulting from exposure to Dox in male and female juvenile rats. Dox significantly reduced body mass and the addition of Ang-(1-7) had no effect. However, adjunct Ang-(1-7) prevented Dox-mediated diastolic dysfunction, including markers of decreased passive filling as measured by reduced early diastole mitral valve flow velocity peak (E) (p
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 21, 2020 Category: Physiology Authors: Rahimi O, Kirby J, Varagic J, Westwood BM, Tallant EA, Gallagher PE Tags: Am J Physiol Heart Circ Physiol Source Type: research

Cardiac-specific inactivation of Prdm16 effects cardiac conduction abnormalities and cardiomyopathy-associated phenotypes.
Abstract A variant in the PRDM16 locus has been correlated with QRS duration in an electrocardiogram genomewide association study, and the deletion of PRDM16 has been implicated as a causal factor of the dilated cardiomyopathy that is linked to 1p36 deletion syndrome. We aimed to determine how a null mutation of Prdm16 affects cardiac function and study the underlying mechanism of the resulting phenotype in an appropriate mouse model. We used cardiac-specific Prdm16 conditional knockout mice to examine cardiac function by electrocardiography. QRS duration and QTc interval increased significantly in cardiac-specifi...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 21, 2020 Category: Physiology Authors: Nam JM, Lim JE, Ha TW, Oh B, Kang JO Tags: Am J Physiol Heart Circ Physiol Source Type: research

Cerebrovascular carbon dioxide reactivity and flow mediated dilation in young healthy South Asian and Caucasian European men.
Abstract South Asians living in the UK have a 1.5-fold greater risk of ischemic stroke than the general population. Impaired cerebrovascular carbon dioxide (CO2) reactivity is an independent predictor of ischemic stroke and cardiovascular mortality. We sought to test the hypothesis that cerebrovascular CO2 reactivity is reduced in South Asians. Middle cerebral artery blood velocity (MCA Vm) was measured at rest and during stepwise changes in partial pressure of end-tidal CO2 (PETCO2) in South Asian (n=16) and Caucasian European (n=18) men that were, young (~20 years), healthy and living in the UK. Incremental hype...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 21, 2020 Category: Physiology Authors: Junejo RT, May S, Alsalahi S, Alali M, Ogoh S, Fisher JP Tags: Am J Physiol Heart Circ Physiol Source Type: research

Pathogenic mechanisms and the potential of drug therapies for aortic aneurysm.
Abstract Aortic aneurysm is a permanent focal dilation of the aorta. It is usually an asymptomatic disease, but can lead to sudden death due to aortic rupture. Aortic aneurysm-related mortalities are estimated at approximately 200,000 deaths per year worldwide. Since no pharmacological treatment has been found to be effective so far, surgical repair remains the only treatment for aortic aneurysm. Aortic aneurysm results from changes in the aortic wall structure due to loss of smooth muscle cells and degradation of the extracellular matrix, and can form in different regions of the aorta. Research over the past deca...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 21, 2020 Category: Physiology Authors: Liu B, Granville DJ, Golledge J, Kassiri Z Tags: Am J Physiol Heart Circ Physiol Source Type: research

Transmural Variation in Microvascular Remodeling Following Percutaneous Revascularization of a Chronic Coronary Stenosis in Swine.
Abstract Remodeling of the coronary microcirculation is known to occur distal to a chronic coronary stenosis, but the reversibility of these changes and their functional significance on maximum myocardial perfusion before and after revascularization is unknown. Accordingly, swine instrumented with a chronic silastic stenosis on the left anterior descending coronary artery to produce hibernating myocardium underwent percutaneous coronary intervention (PCI; n=8) and were compared to animals with a persistent stenosis (n=8) as well as sham controls (n=6). Stenotic animals demonstrated an increased subendocardial arte...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 14, 2020 Category: Physiology Authors: Weil BR, Suzuki G, Canty JM Tags: Am J Physiol Heart Circ Physiol Source Type: research

Alteration of Cardiolipin Biosynthesis and Remodeling in Single Right Ventricle Congenital Heart Disease.
Abstract Despite advances in both medical and surgical therapies, individuals with single ventricle heart disease (SV) remain at high risk for the development of heart failure (HF). However, the molecular mechanisms underlying remodeling and eventual HF in SV patients are poorly characterized. Cardiolipin (CL), an inner mitochondrial membrane phospholipid, is critical for proper mitochondrial function, and abnormalities in CL content and composition are known in various cardiovascular disease etiologies. The purpose of this study was to investigate myocardial CL content and composition in failing and non-failing s...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 14, 2020 Category: Physiology Authors: Garcia AM, McPhaul JC, Sparagna GC, Jeffrey DA, Jonscher RL, Patel S, Sucharov CC, Stauffer BL, Miyamoto SD, Chatfield KC Tags: Am J Physiol Heart Circ Physiol Source Type: research

The role of oxytocin and vasopressin in the pathophysiology of heart failure in pregnancy and in fetal and neonatal life.
Abstract Pregnancy and early life create specific psychosomatic challenges for the mother and child, such as changes in hemodynamics, resetting of the water-electrolyte balance, hypoxia, pain and stress that all play an important role in the regulation of the release of oxytocin and vasopressin. Both these hormones regulate the water-electrolyte balance and cardiovascular functions, maturation of the cardiovascular system, and cardiovascular responses to stress. These aspects may be of particular importance in a state of emergency, such as hypertension in the mother or severe heart failure in the child. In this re...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 14, 2020 Category: Physiology Authors: Szczepanska-Sadowska EK, Cudnoch-Jedrzejewska A, Wsol A Tags: Am J Physiol Heart Circ Physiol Source Type: research

DNA Damage-Free iPS Cells Exhibit Potential to Yield Competent Cardiomyocytes.
Abstract DNA damage accrued in iPS-derived cardiomyocytes (iPS-CMs) during in vitro culture practices lessens their clinical potentials for therapy. We determined whether DNA damage-free iPSCs (DdF-iPS) can be selected using stabilization of p53, transcription factor that promotes apoptosis in DNA damaged cells, and differentiate them into functionally competent DdF-cardiomyocytes (DdF-CM). p53 was activated using Nutlin-3a in iPSCs to selectively kill the DNA damaged cells, and the stable DdF cells were cultured further and differentiated into CM. Both DdF-iPSCs and DdF-CMs were then characterized. We observed a ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 14, 2020 Category: Physiology Authors: Miller JM, Mardhekar NM, Pretorius D, Krishnamurthy P, Rajasekaran NS, Zhang J, Kannappan R Tags: Am J Physiol Heart Circ Physiol Source Type: research

Gut Microbiome of a Porcine Model of Metabolic Syndrome and HF-pEF.
Abstract Metabolic syndrome (MetS) is a combination of cardiovascular risk factors including obesity, hyperlipidemia, hypertension, insulin resistance, non-alcoholic fatty liver disease and diastolic heart failure. This syndrome has been identified as one of the greatest global health challenges of the 21st century. Herein, we examine in a porcine model of diet-induced MetS whether cardiovascular, metabolic, gut microbiota and functional metataxonomic changes mimic those observed in human studies. Landrace pigs with mineralocorticoid-induced hypertension fed a high-fat, salt and sugar diet (HFD) over 12 weeks were...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 7, 2020 Category: Physiology Authors: O'Donovan AN, Herisson FM, Fouhy F, Ryan PM, Whelan D, Johnson CN, Cluzel G, Ross RP, Stanton C, Caplice NM Tags: Am J Physiol Heart Circ Physiol Source Type: research

MitoQ regulates redox-related non-coding RNAs to preserve mitochondrial network integrity in pressure overload heart failure.
Abstract Evidence suggests that mitochondrial network integrity is impaired in cardiomyocytes from failing hearts. While oxidative stress has been implicated in heart failure (HF)-associated mitochondrial remodeling, the effect of mitochondrial-targeted antioxidants, such as mitoquinone (MitoQ), on the mitochondrial network in a model of heart failure (HF) (e.g. pressure overload) has not been demonstrated. Furthermore, the mechanism of this regulation is not completely understood with an emerging role for post-transcriptional regulation via long non-coding RNAs (lncRNA). We hypothesize that MitoQ preserves mitoch...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 31, 2020 Category: Physiology Authors: Kim S, Song J, Ernst P, Latimer MN, Ha CM, Goh KY, Ma W, Rajasekaran NS, Zhang J, Liu XM, Prabhu S, Qin G, Wende AR, Young ME, Zhou L Tags: Am J Physiol Heart Circ Physiol Source Type: research

A Stepwise Approach to Resolving Small Ionic Currents in Vascular Tissue.
This study describes a stepwise approach to dissect small ionic currents at physiological VM using endothelial and smooth muscle cells freshly isolated from rat cerebral arteries. We highlight three critical steps, beginning with the voltage clamping of vascular cells bathed in physiological solutions while maintaining a giga-ohm seal. KIR channels are then inhibited (micromolar Ba2+) so that a difference current can be created, once Ba2+ traces are corrected for the changing seal resistance and subtle instrument drift, pulling the reversal potential rightward. The latter is a new procedure and entails the alignment of who...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 31, 2020 Category: Physiology Authors: Sancho M, Hald BO, Welsh DG Tags: Am J Physiol Heart Circ Physiol Source Type: research

Antithrombotic Effects of Heme-Degrading and Heme-Binding Proteins.
This study examined whether induction of HO-1 or administration of its products reduces thrombosis. Venous HO-1 upregulation by gene delivery reduced clot size, as did products of HO activity, biliverdin and carbon monoxide. Induction of HO-1 by hemin reduced clot formation, clot size, and upregulation of PAI-1 that occurs in the IVCL model, while leaving uPA and tPA expression unaltered. The reductive effect of hemin on clot size required HO activity. The IVCL model exhibited relatively high concentrations of heme which peaked just prior to maximum clot size, then declined as clot size decreased. Administration of hemin d...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 31, 2020 Category: Physiology Authors: Nath KA, Grande JP, Belcher JD, Garovic VD, Croatt AJ, Hillestad ML, Barry MA, Nath MC, Regan RF, Vercellotti GM Tags: Am J Physiol Heart Circ Physiol Source Type: research

A recent history of preeclampsia is associated with elevated central pulse wave velocity and muscle sympathetic outflow.
Abstract Preeclampsia is associated with the development of cardiovascular diseases later in life. To investigate this phenomenon, we compared established markers of cardiovascular dysregulation between previously preeclamptic women (PPE; n=12; 13±6 months postpartum; 34±6 y) and women who had previously had an uncomplicated pregnancy (CTRL; n=12; 15±4 months postpartum; 29±3 y). We hypothesized that PPE would present with elevated arterial stiffness (assessed as central and peripheral pulse wave velocity) and muscle sympathetic nerve activity (MSNA; microneurography), and blunted baror...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 31, 2020 Category: Physiology Authors: Usselman CW, Adler TE, Coovadia Y, Leone C, Paidas MJ, Stachenfeld NS Tags: Am J Physiol Heart Circ Physiol Source Type: research

A 6-month systems toxicology inhalation study in ApoE-/- mice demonstrates reduced cardiovascular effects of E-vapor aerosols compared to cigarette smoke.
Abstract Smoking cigarettes is harmful to the cardiovascular system. Considerable attention has been paid to the reduced harm potential of alternative nicotine-containing inhalable products such as e-cigarettes. We investigated the effects of E-vapor aerosols or cigarette smoke (CS) on atherosclerosis progression, cardiovascular function, and molecular changes in the heart and aorta of female ApoE-/- mice. The mice were exposed to aerosols from three different E-vapor formulations: (1) carrier (propylene glycol and vegetable glycerol), (2) base (carrier and nicotine) or (3) test (base and flavor) or to CS from 3R4...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 24, 2020 Category: Physiology Authors: Szostak J, Wong ET, Titz B, Lee T, Wong SK, Low T, Lee KM, Zhang J, Kumar A, Schlage WK, Guedj E, Phillips B, Leroy P, Buettner A, Xiang Y, Martin F, Sewer A, Kuczaj A, Ivanov NV, Luettich K, Vanscheeuwijck P, Peitsch MC, Hoeng J Tags: Am J Physiol Heart Circ Physiol Source Type: research

Cigarette Smoke Extract Induces Ferroptosis in Vascular Smooth Muscle Cells.
Abstract Cigarette smoking is a major risk factor for aortic aneurysm and dissection; however, no causative link between smoking and these aortic disorders has been proven. In the present study, we investigated the mechanism by which cigarette smoke affects vascular wall cells and found that cigarette smoke extract (CSE) induced a novel form of regulated cell death termed ferroptosis in VSMCs. CSE markedly induced cell death in A7r5 cells and primary rat VSMCs, but not in endothelial cells, which was completely inhibited by specific ferroptosis inhibitors (Ferrostatin-1 [Fer-1] and Liproxstatin-1) and an iron chel...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 24, 2020 Category: Physiology Authors: Sampilvanjil A, Karasawa T, Yamada N, Komada T, Higashi T, Baatarjav C, Watanabe S, Kamata R, Ohno N, Takahashi M Tags: Am J Physiol Heart Circ Physiol Source Type: research

Cardiac sympathetic nerve transdifferentiation reduces action potential heterogeneity after myocardial infarction.
Abstract Cardiac sympathetic nerves undergo cholinergic transdifferentiation following reperfused myocardial infarction (MI), whereby the sympathetic nerves release both norepinephrine (NE) and acetylcholine (ACh). The functional electrophysiological consequences of post-MI transdifferentiation have never been explored. We performed MI or sham surgery in wild-type (WT) mice and mice in which choline acetyltransferase (ChAT) was deleted from adult noradrenergic neurons (KO). Electrophysiological activity was assessed with optical mapping of action potentials (AP) and intracellular Ca2+ transients (CaT) in innervate...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 24, 2020 Category: Physiology Authors: Wang L, Olivas A, Francis Stuart SD, Tapa S, Blake M, Woodward WR, Habecker BA, Ripplinger CM Tags: Am J Physiol Heart Circ Physiol Source Type: research