Angiotensin II type 1 receptor is involved in flow-induced vasomotor responses of isolated middle cerebral arteries. Role of oxidative stress
This study aimed to determine the mechanosensing role of angiotensin II type 1 receptor (AT1R) in flow-induced dilation (FID) and oxidative stress production in middle cerebral arteries (MCA) of Sprague-Dawley rats. Eleven-weeks old, healthy male Sprague-Dawley rats on a standard diet were given the AT1R blocker losartan (1 mg/mL) in drinking water (losartan group) or tap water (control group) ad libitum for 7 days. Blockade of AT1R attenuated FID and acetylcholine-induced dilations was compared to control group. Nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) and cyclooxygenase inhibit...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 5, 2021 Category: Physiology Authors: Ivana Jukic Zrinka Mihaljevic Anita Matic Martina Mihalj Natasa Kozina Kristina Selthofer-Relatic Dubravka Mihaljevic Akos Koller Ivana Tartaro Bujak Ines Drenjancevic Source Type: research

Geometrical remodeling of the mitral and tricuspid annuli in response to exercise training: a 3D echocardiographic study in elite athletes
Am J Physiol Heart Circ Physiol. 2021 Mar 5. doi: 10.1152/ajpheart.00877.2020. Online ahead of print.ABSTRACTIntense exercise exposes the heart to significant hemodynamic demands, resulting in adaptive changes in cardiac morphology and function. Nevertheless, the athletic adaptation of the atrioventricular valves remains to be elucidated. Our study aimed to characterize the geometry of mitral (MA) and tricuspid (TA) annuli in elite athletes using 3D echocardiography. Thirty-four athletes presented with functional mitral regurgitation (FMR) were retrospectively identified and compared to 34 athletes without MR, and 34 healt...
Source: American Journal of Physiology. Heart and Circulatory Physiology - March 5, 2021 Category: Physiology Authors: Alexandra Fabian B álint Károly Lakatos Marton Tokodi Anna Reka Kiss N óra Sydó Emese Csulak Erika Kispal M áté Babity Andrea Szucs Orsolya Kiss B éla Merkely Attila Kov ács Source Type: research

Retraction for Sarkar et al., volume 287, 2004, p. H107-H117.
Authors: PMID: 33595374 [PubMed] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 19, 2021 Category: Physiology Tags: Am J Physiol Heart Circ Physiol Source Type: research

Retraction for Gupta et al., volume 297, 2009, p. H627-H636.
Authors: PMID: 33595375 [PubMed] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 19, 2021 Category: Physiology Tags: Am J Physiol Heart Circ Physiol Source Type: research

Retraction for Gupta et al., volume 289, 2005, p. H20-H29.
Authors: PMID: 33595376 [PubMed] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 19, 2021 Category: Physiology Tags: Am J Physiol Heart Circ Physiol Source Type: research

Corrigendum for Venkatakrishnan et al., volume 294, 2008, p. H1736-H1744.
Authors: PMID: 33595377 [PubMed] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 19, 2021 Category: Physiology Tags: Am J Physiol Heart Circ Physiol Source Type: research

Enhanced endothelial barrier function by monoclonal antibody activation of vascular endothelial cadherin.
Abstract Excessive vascular permeability occurs in inflammatory disease processes. Vascular endothelial cadherin (VE-cadherin) is an adhesion protein that controls vascular permeability. We identified monoclonal antibodies (mAbs) to human VE-cadherin that activate cell adhesion and inhibit the increased permeability of endothelial cell monolayers induced by thrombin receptor activator peptide-6 (TRAP-6). Two mAbs, 8A12c and 3A5a, reduce permeability while an inhibitory mAb, 2E11d, enhances permeability. Activating mAbs also reduce permeability induced by tumor necrosis factor-α (TNF-α), and vascular en...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 12, 2021 Category: Physiology Authors: Park KS, Schecterson L, Gumbiner BM Tags: Am J Physiol Heart Circ Physiol Source Type: research

Exosomal microRNAs in the development of essential hypertension and its potential as biomarkers.
Abstract MicroRNAs (miRNAs) are small regulatory molecules that are involved in post-transcriptional modifications. These non-coding RNAs are usually ferried by extracellular carriers such as exosomes or other protein and lipid carriers inside a range of body fluids including plasma and urine. Due to their ability to withstand harsh external conditions, exosomal miRNAs possess enormous potentials as non-invasive disease biomarkers for, notably hypertension, whereby exosomal miRNAs have been implicated in its pathophysiological processes. More importantly, alterations in the microenvironment as a result of disease ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 12, 2021 Category: Physiology Authors: Tan PPS, Hall D, Chilian WM, Chia YC, Mohd Zain S, Lim HM, Kumar DN, Ching SM, Low TY, Md Noh MF, Pung YF Tags: Am J Physiol Heart Circ Physiol Source Type: research

Angiotensin-II type 1 receptor mediates pulmonary hypertension and right ventricular remodeling induced by inhaled nicotine.
Abstract Use of electronic cigarettes is rapidly increasing among youth and young adults, but little is known regarding the long-term cardiopulmonary health impacts of these nicotine-containing devices. Our group has previously demonstrated that chronic, inhaled nicotine induces pulmonary hypertension (PH) and right ventricular (RV) remodeling in mice. These changes were associated with upregulated RV angiotensin-converting enzyme (ACE). Angiotensin-II receptor blockers (ARBs) have been shown to reverse cigarette smoking-induced PH in rats. ACE inhibitor and ARB use in a large retrospective PH patient cohort is as...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 12, 2021 Category: Physiology Authors: Fried ND, Morris TM, Whitehead A, Lazartigues E, Yue X, Gardner JD Tags: Am J Physiol Heart Circ Physiol Source Type: research

FoxO1 is required for physiological cardiac hypertrophy induced by exercise but not by constitutively active PI3K.
Abstract The insulin-like growth factor 1 receptor (IGF1R) and phosphoinositide 3-kinase p110a (PI3K) are critical regulators of exercise-induced physiological cardiac hypertrophy, and provide protection in experimental models of pathological remodeling and heart failure. Forkhead box class O1 (FoxO1) is a transcription factor which regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K activation in vitro, but its role in physiological hypertrophy in vivo was unknown. We generated cardiomyocyte-specific FoxO1 knockout (cKO) mice and assessed the phenotype under basal conditions and settings of physiological...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 12, 2021 Category: Physiology Authors: Weeks KL, Tham YK, Yildiz SG, Alexander Y, Donner DG, Kiriazis H, Harmawan CA, Hsu AT, Bernardo BC, Matsumoto A, DePinho RA, Abel ED, Woodcock EA, McMullen JR Tags: Am J Physiol Heart Circ Physiol Source Type: research

Left Ventricular Diastolic Dysfunction and Exercise Intolerance in Obese Heart Failure with Preserved Ejection Fraction.
This study tested the hypothesis that early left ventricular (LV) relaxation is impaired in older obese heart failure with preserved ejection fraction (HFpEF) patients, and related to decreased peak exercise oxygen uptake (peak VO2). LV strain and strain rate were measured by feature tracking of magentic resonance cine images in 79 older obese HFpEF patients (mean age: 66 years; mean BMI: 38 kg/m2) and 54 healthy control participants. LV diastolic strain rates were indexed to cardiac preload as estimated by echocardiography derived diastolic filling pressures (E/e'), and correlated to peak VO2. LV circumferential early dia...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 12, 2021 Category: Physiology Authors: Samuel TJ, Kitzman DW, Haykowsky MJ, Upadhya B, Brubaker P, Nelson MB, Hundley WG, Nelson MD Tags: Am J Physiol Heart Circ Physiol Source Type: research

Electronic Cigarette Solvents, Pulmonary Irritation and Endothelial Dysfunction:Role of Acetaldehyde and Formaldehyde.
This study indicates that FA levels in tobacco product-derived aerosols should be regulated to levels that do not induce biomarkers of cardiopulmonary harm. There remains a need for reliable biomarkers of exposure to inhaled FA and AA. PMID: 33543686 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 5, 2021 Category: Physiology Authors: Jin L, Lynch J, Richardson A, Lorkiewicz P, Srivastava S, Theis W, Shirk G, Hand A, Bhatnagar A, Srivastava S, Conklin DJ Tags: Am J Physiol Heart Circ Physiol Source Type: research

Demonstration of age-related blood-brain barrier disruption and cerebromicrovascular rarefaction in mice by two-photon microscopy & optical coherence tomography.
Demonstration of age-related blood-brain barrier disruption and cerebromicrovascular rarefaction in mice by two-photon microscopy & optical coherence tomography. Am J Physiol Heart Circ Physiol. 2021 Feb 05;: Authors: Nyúl-Tóth Á, Tarantini S, Delfavero J, Yan F, Balasubramanian P, Yabluchanskiy A, Ahire C, Kiss T, Csipo T, Lipecz A, Farkas AE, Wilhelm I, Krizbai IA, Tang Q, Csiszar A, Ungvari ZI Abstract Age-related blood-brain barrier disruption and cerebromicrovascular rarefaction contribute importantly to the pathogenesis of both vascular cognitive impairment and dementia ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - February 5, 2021 Category: Physiology Authors: Nyúl-Tóth Á, Tarantini S, Delfavero J, Yan F, Balasubramanian P, Yabluchanskiy A, Ahire C, Kiss T, Csipo T, Lipecz A, Farkas AE, Wilhelm I, Krizbai IA, Tang Q, Csiszar A, Ungvari ZI Tags: Am J Physiol Heart Circ Physiol Source Type: research

Oxidized phosphatidylcholines trigger ferroptosis in cardiomyocytes during ischemia/reperfusion injury.
Abstract Myocardial ischemia/reperfusion (I/R) injury increases the generation of oxidized phosphatidylcholines (OxPCs) which results in cell death. However, the mechanism by which OxPCs mediate cell death is largely unknown. The aim of this study was to determine the mechanisms by which OxPC triggers cardiomyocyte cell death during reperfusion injury. Cardiomyocyte viability, bioenergetic response and calcium transients were determined in the presence of OxPCs. Fragmented OxPCs resulted in a decrease in cell viability with POVPC and PONPC having the most potent cardiotoxic effect in both a concentration and time dependent manner (P
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 29, 2021 Category: Physiology Authors: Stamenkovic A, O'Hara KA, Nelson DC, Maddaford TG, Edel AL, Maddaford G, Dibrov E, Aghanoori M, Kirshenbaum LA, Fernyhough P, Aliani M, Pierce GN, Ravandi A Tags: Am J Physiol Heart Circ Physiol Source Type: research

Characterization of βARKct engineered extracellular vesicles and model specific cardioprotection.
In this study we tested whether βARKct-CDC EVs would be efficacious when applied to stressed myocytes in vitro and in vivo. When isolated EVs from βARKct-CDC and control GFP-CDC were added to cardiomyocytes in culture, they both protected against hypoxia-induced apoptosis. We tested whether these EVs could protect the mouse heart in vivo following exposure either to myocardial infarction (MI) or acute catecholamine toxicity. Both types of EVs significantly protected against ischemic injury and improved cardiac function after MI compared to mice treated with EVs from mouse embryonic fibroblasts, however βARKc...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 29, 2021 Category: Physiology Authors: Kwon JS, Schumacher SM, Gao E, Chuprun JK, Ibetti J, Roy R, Khan M, Kishore R, Koch WJ Tags: Am J Physiol Heart Circ Physiol Source Type: research

Cardiovascular Effects of Air Pollution: Current Evidence from Animal and Human Studies.
CONCLUSIONS: The current review underscores the relevance of air pollution as a global health concern that affects cardiovascular health. More rigorous standardsare needed to reduce the cardiovascular disease burden imposed by air pollution. Continued research on the health impact of air pollution is needed to provide further insight. PMID: 33513082 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 29, 2021 Category: Physiology Authors: Lederer AM, Fredriksen PM, Nkeh-Chungag BN, Everson F, Strijdom H, de Boever P, Goswami N Tags: Am J Physiol Heart Circ Physiol Source Type: research

Cellular signalling crosstalk between different cardiac cell populations - An insight into the role of exosomes in the heart diseases and therapy.
Abstract Exosomes are a subgroup of extracellular bilayer membrane nanovesicles that are enriched in a variety of bioactive lipids, receptors, transcription factors, surface proteins, DNA and noncoding RNAs. They have been well-recognised to play essential roles in mediating intercellular signalling by delivering bioactive molecules from host cells to regulate the physiological processes of recipient cells. In the context of heart diseases, accumulating studies have indicated that exosome-carried cellular proteins and noncoding RNA derived from different types of cardiac cells, including cardiomyocytes, fibroblast...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 29, 2021 Category: Physiology Authors: Nguyen BY, Azam T, Wang X Tags: Am J Physiol Heart Circ Physiol Source Type: research

Metformin impairs homing ability and efficacy of mesenchymal stem cells for cardiac repair in streptozotocin-induced diabetic cardiomyopathy in rats.
In this study, we investigated the effect of metformin on the efficacy of stem cell therapy in a diabetic cardiomyopathy animal model using streptozotocin (STZ) in male Wistar rats. To comprehend the effect of metformin on the efficacy of BM-MSCs, we transplanted BM-MSCs (1 million cells/rat) with or without metformin. Our data demonstrate that transplantation of BM-MSCs prevented cardiac fibrosis and promoted angiogenesis in diabetic hearts. However, metformin supplementation downregulated BM-MSCs mediated cardioprotection. Interestingly, both BM-MSCs and metformin treatment individually, improved cardiac function with no...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 29, 2021 Category: Physiology Authors: Ammar HI, Shamseldeen AM, Shoukry HS, Ashour H, Kamar SS, Rashed LA, Fadel M, Srivastava A, Dhingra S Tags: Am J Physiol Heart Circ Physiol Source Type: research

Paraquat herbicide diminishes chemoreflex sensitivity, induces cardiac autonomic imbalance and impair cardiac function in rats.
PARAQUAT HERBICIDE DIMINISHES CHEMOREFLEX SENSITIVITY, INDUCES CARDIAC AUTONOMIC IMBALANCE AND IMPAIR CARDIAC FUNCTION IN RATS. Am J Physiol Heart Circ Physiol. 2021 Jan 29;: Authors: Pereyra KV, Schwarz K, Andrade DC, Toledo C, Rios-Gallardo A, Díaz-Jara E, Bastias SS, Ortiz F, Ortolani D, Del Rio R Abstract Paraquat (PQT) herbicide is widely used in agricultural practices despite is highly toxic to humans. It has been proposed that PQT exposure may promote cardiorespiratory impairment. However, the physiological mechanisms involved in cardiorespiratory dysfunction following PQT exposure are p...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 29, 2021 Category: Physiology Authors: Pereyra KV, Schwarz K, Andrade DC, Toledo C, Rios-Gallardo A, Díaz-Jara E, Bastias SS, Ortiz F, Ortolani D, Del Rio R Tags: Am J Physiol Heart Circ Physiol Source Type: research

Artificial Intelligence for a Personalized Diagnosis and Treatment of Atrial Fibrillation.
z-Avilés F Abstract Although Atrial Fibrillation (AF) is the most common cardiac arrhythmia, its early identification, diagnosis, and treatment is still challenging. Due to its heterogeneous mechanisms and risk-factors, targeting an individualized treatment of AF demands a large amount of patient data to identify specific patterns. Artificial Intelligence (AI) algorithms are particularly well suited for treating high-dimensional data, predicting outcomes and, eventually, optimizing strategies for patient management. The analysis of large patient samples combining different sources of information such as blo...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 29, 2021 Category: Physiology Authors: Sánchez de la Nava AM, Atienza F, Bermejo J, Fernández-Avilés F Tags: Am J Physiol Heart Circ Physiol Source Type: research

Evaluation of right coronary vascular dysfunction in severe pulmonary hypertensive rats using synchrotron radiation microangiography.
CONCLUSION: We found impairment of vasodilator responses in the RCA of severe PH rat models. Endothelin-1 activation in the RCA plays a major role in impaired vascular function in PH rats and is partially restored by ERA treatment. Treatment of PH with ERA may improve RV function in part by indirectly attenuating right heart afterload and in part by associated improvements in right coronary endothelial function. PMID: 33481696 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 22, 2021 Category: Physiology Authors: Inagaki T, Pearson JT, Tsuchimochi H, Schwenke DO, Saito S, Higuchi T, Masaki T, Umetani K, Shirai M, Nakaoka Y Tags: Am J Physiol Heart Circ Physiol Source Type: research

Radial-Digital pulse wave velocity: a non-invasive method for assessing stiffness of small conduit arteries.
zii M Abstract BACKGROUND: Pulse wave velocity (PWV) is used to evaluate regional stiffness of large and medium-sized arteries. Here, we examine the feasibility and reliability of radial-digital PWV (RD-PWV) as a measure of regional stiffness of small conduit arteries, and its response to changes in hydrostatic pressure. METHODS AND RESULTS: In 29 healthy subjects, we used Complior Analyse piezoelectric probes to record arterial pulse wave at radial artery and tip of the index. We determined transit time by second-derivative and intersecting-tangents using the device-embedded algorithms, in house Matlab-based...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 22, 2021 Category: Physiology Authors: Obeid H, Fortier C, Garneau CA, Paré M, Boutouyrie P, Bruno RM, Khettab H, Goupil R, Agharazii M Tags: Am J Physiol Heart Circ Physiol Source Type: research

A novel model of chronic limb ischemia to therapeutically evaluate the angiogenic effects of drug candidates.
Abstract Critical limb ischemia (CLI) is a severe state of peripheral artery disease with high unmet clinical needs. Further, there are no effective treatment options for CLI patients. Based on preclinical study results, predicting the clinical efficacy of CLI treatments is typically difficult because conventional hindlimb ischemia (HLI) rodent models display spontaneous recovery from ischemia, which is not observed in CLI patients. Therefore, we aimed to develop a novel chronic and severe HLI model to properly evaluate the therapeutic effects of drug candidates for CLI. Severe HLI mice (Type-N) were generated by ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 22, 2021 Category: Physiology Authors: Shimatani K, Sato H, Saito A, Sasai M, Watanabe K, Mizukami K, Kamohara M, Miyagawa S, Sawa Y Tags: Am J Physiol Heart Circ Physiol Source Type: research

Postpartum microvascular functional alterations following severe preeclampsia.
The objective of this study was to examine postpartum microvascular endothelial function in women after a pregnancy complicated by preeclampsia. Women with previous preeclampsia (n=30) and normotensive controls (n=30) between 6 months and 5 years postpartum were recruited. Severity of preeclampsia (severe (n=16) and mild (n=14)) was determined by standardized chart review. Microvascular reactivity in the forearm was measured with laser speckle contrast imaging, coupled with iontophoresis; endothelium-dependent and -independent vasodilation was induced with 1% acetylcholine and sodium nitroprusside solutions, respectively. ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 22, 2021 Category: Physiology Authors: Barr LC, Pudwell J, Smith GN Tags: Am J Physiol Heart Circ Physiol Source Type: research

Elevated post-ischemic tissue injury and leukocyte-endothelial adhesive interactions in mice with global deficiency in caveolin-2: role of PAI-1.
In conclusion, our data suggest that Cav-2 protein alleviates tissue injury in response to I/R by dampening PAI-1 protein levels and thereby reducing leukocyte-endothelial adhesive interactions. PMID: 33481700 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 22, 2021 Category: Physiology Authors: Liu Y, Wang M, Wang D, Fay WP, Korthuis RJ, Sowa G Tags: Am J Physiol Heart Circ Physiol Source Type: research

Adaptation to 5 weeks of intermittent local vascular pressure increments; mechanisms to be considered in the development of primary hypertension?
gård R Abstract The aims were to study effects of iterative exposures to moderate elevations of local intravascular pressure on arterial/arteriolar stiffness and plasma levels of vasoactive substances. Pressures in the vasculature of an arm were increased by 150 mmHg in healthy men (n=11) before and after a 5-wk regimen, during which the vasculature in one arm was exposed to fifteen 40-min sessions of moderately increased transmural pressure (+65 to +105 mmHg). This vascular pressure training and the pressure-distension determinations were conducted by exposing the subjects arm versus remaining part of the b...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 22, 2021 Category: Physiology Authors: Eiken O, Elia A, Sköldefors H, Sundblad P, Keramidas ME, Kölegård R Tags: Am J Physiol Heart Circ Physiol Source Type: research

Inorganic Arsenic Induces Sex-Dependent Pathological Hypertrophy in the Heart.
Abstract Arsenic exposure through drinking water is widespread and well-associated with adverse cardiovascular outcomes, yet the pathophysiological mechanisms by which inorganic arsenic (iAS) induces these effects are largely unknown. Recently, an epidemiological study in an American population with a low burden of cardiovascular risk factors found that iAS exposure was associated with altered left ventricular geometry. Considering the possibility that iAS directly induces cardiac remodeling independent of hypertension, we investigated the impact of an environmentally relevant iAS exposure on the structure and fun...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 22, 2021 Category: Physiology Authors: Kabir R, Sinha P, Mishra S, Ebenebe OV, Taube N, Oeing CU, Keceli G, Chen R, Paolocci N, Rule AM, Kohr MJ Tags: Am J Physiol Heart Circ Physiol Source Type: research

TMEM16A channel upregulation in arterial smooth muscle cells produces vasoconstriction during diabetes.
Abstract The pathological involvement of anion channels in vascular dysfunction that occurs during type 2 diabetes (T2D) is unclear. Here, we tested the hypothesis that TMEM16A, a calcium (Ca2+)-activated chloride (Cl-) channel, contributes to modifications in arterial contractility during T2D. Our data indicate that T2D increased TMEM16A mRNA in arterial smooth muscle cells (myocytes) and total and surface TMEM16A protein in resistance-size arteries of mice. To examine vascular cell types in which TMEM16A expression is upregulated, we generated a tamoxifen-inducible, smooth muscle-specific TMEM16A knockout (TMEM1...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 15, 2021 Category: Physiology Authors: Leo MD, Peixoto-Neves D, Yin W, Raghavan S, Muralidharan P, Mata-Daboin A, Jaggar JH Tags: Am J Physiol Heart Circ Physiol Source Type: research

Inorganic nitrate supplementation attenuates conduit artery retrograde and oscillatory shear in older adults.
Abstract Aging causes deleterious changes in resting conduit artery shear patterns and reduced blood flow during exercise partially attributable to reduced nitric oxide (NO). Inorganic nitrate increases circulating NO bioavailability and may therefore improve age-associated changes in shear rate as well as exercise hyperemia. 10 older adults (67±3yrs) consumed 4.03mmol nitrate and 0.29mmol nitrite (active) or devoid of both (placebo) daily for 4wks in randomized, double-blinded, crossover fashion. Brachial artery diameter (D) and blood velocity (Vmean) were measured via Doppler ultrasound at rest for the ch...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 15, 2021 Category: Physiology Authors: Casey DP, Bock JM Tags: Am J Physiol Heart Circ Physiol Source Type: research

Pannexin 1 Channels Control the Hemodynamic Response to Hypoxia by Regulating O2-Sensitive Extracellular ATP in Blood.
Abstract Pannexin1 (Panx1) channels export ATP and may contribute to increased concentration of the vasodilator ATP in plasma during hypoxia in vivo. We hypothesized that Panx1 channels and associated ATP export contributes to hypoxic vasodilation, a mechanism that facilitates the matching of oxygen delivery to tissue metabolic demand. Male and female mice devoid of Panx1 (Panx1-/-) and wild-type controls (WT) were anesthetized, mechanically ventilated, and instrumented with a carotid artery catheter or femoral artery flow transducer for hemodynamic and plasma ATP monitoring during inhalation of 21% (normoxia) or ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 15, 2021 Category: Physiology Authors: Kirby BS, Sparks MA, Lazarowski ER, Lopez Domowicz DA, Zhu H, McMahon TJ Tags: Am J Physiol Heart Circ Physiol Source Type: research

Mavacamten preserved length-dependent contractility and improved diastolic function in human engineered heart tissue.
Abstract Comprehensive functional characterization of cardiac tissue includes investigation of length and load dependence. Such measurements have been slow to develop in engineered heart tissues (EHTs), whose mechanical characterizations have been limited primarily to isometric and near-isometric behaviors. A more realistic assessment of myocardial function would include force-velocity curves to characterize power output and force-length loops mimicking the cardiac cycle to characterize work output. We developed a system that produces force-velocity curves and work loops in human EHTs using an adaptive iterative c...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 15, 2021 Category: Physiology Authors: Sewanan LR, Shen S, Campbell SG Tags: Am J Physiol Heart Circ Physiol Source Type: research

The impact of the 24-hour movement spectrum on vascular remodeling in older men and women: a review.
Abstract Aging is associated with increased risk of cardiovascular and cerebrovascular events, which are preceded by early, negative remodeling of the vasculature. Low physical activity is a well-established risk factor associated with the incidence and development of disease. However, recent physical activity literature indicates the importance of considering the 24-hour movement spectrum. Therefore, the purpose of this review was to examine the impact of the 24-hour movement spectrum, specifically physical activity (aerobic and resistance training), sedentary behaviour, and sleep, on cardiovascular and cerebrova...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 15, 2021 Category: Physiology Authors: Williams JS, Dunford EC, Cheng JL, Moncion K, Valentino SE, Droog CA, Cherubini JM, King TJ, Noguchi KS, Wiley E, Turner JR, Tang A, Al-Khazraji BK, MacDonald MJ Tags: Am J Physiol Heart Circ Physiol Source Type: research

Transient Receptor Potential Vanilloid 4 channel participates in mouse ventricular electrical activity.
CONCLUSION: This study shows for the first time that TRPV4 modulates AP and QTc durations and constitutes thereby a good therapeutical target against long QT-mediated ventricular arrhythmias. PMID: 33449852 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 15, 2021 Category: Physiology Authors: Chaigne S, Cardouat G, Louradour J, Vaillant F, Charron S, Sacher F, Ducret T, Guinamard R, Vigmond E, Hof T Tags: Am J Physiol Heart Circ Physiol Source Type: research

CaMKII δ Met281/282 oxidation is not required for recovery of calcium transients during acidosis.
CONCLUSIONS: Our study shows that oxidative activation of CaMKIId is neither required for recovery of Ca2+-transients during acidosis nor relevant for post-acidic arrhythmias in isolated cardiac myocytes. Moreover, acidosis actually reduces the cytosolic redox potential of isolated cardiac myocytes. Pharmacological inhibition of global CaMKII activity completely prevents recovery of Ca2+-transients and protects from post-acidic arrhythmias in MM-VV myocytes which confirms the relevance of CaMKII activity in the context of acidosis. PMID: 33449853 [PubMed - as supplied by publisher] (Source: American Journal of Physiol...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 15, 2021 Category: Physiology Authors: Kreitmeier KG, Tarnwoski D, Nanadikar MS, Baier MJ, Wagner S, Katschinski DM, Maier LS, Sag CM Tags: Am J Physiol Heart Circ Physiol Source Type: research

Donor specific phenotypic variation in hiPSC cardiomyocyte-derived exosomes impacts endothelial cell function.
Abstract Exosomes are an important mechanism of cell-cell interaction in the cardiovascular system, both in maintaining homeostasis and in stress response. Interindividual differences that alter content in exosomes may play a role in cardiovascular disease pathology. To study the effect of interindividual cardiomyocyte (CM) variation, we characterized exosomal content in phenotypically diverse human induced pluripotent stem cell-derived CMs (hiPSC-CMs). Cell lines were generated from six participants in the HyperGEN cohort: three with left ventricular hypertrophy (LVH) and three with normal left ventricular mass. ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 8, 2021 Category: Physiology Authors: Turner A, Aggarwal P, Matter A, Olson B, Gu CC, Hunt SC, Lewis CE, Arnett DK, Lorier R, Broeckel U Tags: Am J Physiol Heart Circ Physiol Source Type: research

An integrated mathematical model of the cardiovascular and respiratory response to exercise: Model-building and comparison with reported models.
s MÁ Abstract The use of physiological models in medicine allows the evaluation of new hypotheses, development of diagnosis and clinical treatment applications, development of training and medical education tools, as well as medical device design. Although several mathematical models of physiological systems have been presented in the literature, few of them are able to predict the human cardiorespiratory response under physical exercise stimulus adequately. This paper aims to present the building and comparison of an integrated cardiorespiratory model focused on the prediction of the healthy human response...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 8, 2021 Category: Physiology Authors: Sarmiento CA, Hernandez AM, Serna Higuita LY, Mañanas MÁ Tags: Am J Physiol Heart Circ Physiol Source Type: research

New insight in understanding the contribution of SGLT1 in cardiac glucose uptake: evidence for a truncated form in mice and humans.
In conclusion, cardiac SGLT1 does not contribute to overall glucose uptake, probably due to the expression of slc5a1 transcript variant. The inhibitory effect of phlorizin on cardiac glucose uptake is SGLT1-independent and can be explained by GLUT transporter inhibition. These data open new perspectives in understanding the role of SGLT1 in the heart. PMID: 33416451 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 8, 2021 Category: Physiology Authors: Ferté L, Marino A, Battault S, Bultot L, Van Steenbergen A, Bol A, Cumps J, Ginion A, Koepsell H, Dumoutier L, Hue L, Horman S, Bertrand L, Beauloye C Tags: Am J Physiol Heart Circ Physiol Source Type: research

Folic acid prevents functional and structural heart defects induced by prenatal ethanol exposure.
Abstract Increased regurgitant blood flow has been linked to endocardial cushion defects and resultant congenital heart diseases (CHDs). Prenatal alcohol exposure (PAE) has been shown to alter early blood flow resulting in abnormal endocardial cushions and CHDs. Compounds, including folic acid (FA), mitigate PAE effects and prevent CHDs, but few studies have assessed their effects on blood flow. We modeled binge drinking in quail embryos at gastrulation. Embryos were exposed to ethanol alone, FA (3.2 μg/egg) alone, and the two simultaneously. We quantified in cardiac looping stages (equivalent to 4 weeks of hum...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 8, 2021 Category: Physiology Authors: Ford SM, Pedersen CJ, Ford MR, Kim JW, Karunamuni GH, McPheeters MT, Jawaid S, Jenkins MW, Rollins AM, Watanabe M Tags: Am J Physiol Heart Circ Physiol Source Type: research

Sympathetic Transduction in Humans: Recent Advances and Methodological Considerations.
Abstract Since their origin over one half-century ago, microneurographic recordings of sympathetic nerve activity have significantly advanced our understanding of the generation and regulation of central sympathetic outflow in human health and disease. For example, it is now appreciated that a myriad of disease states exhibit chronic sympathetic overactivity, a significant predictor of cardiovascular morbidity and mortality. While microneurographic recordings allow for the direct quantification of sympathetic outflow, they alone do not provide information with respect to the ensuing sympathetically-mediated vasoco...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 8, 2021 Category: Physiology Authors: Young BE, Greaney JL, Keller DM, Fadel PJ Tags: Am J Physiol Heart Circ Physiol Source Type: research

G6PD activity contributes to the regulation of histone acetylation and gene expression in smooth muscle cells and to the pathogenesis of vascular diseases.
Abstract We aimed to determine: 1) the mechanism(s) that enable glucose-6-phosphate dehydrogenase (G6PD) to regulate serum response factor (SRF)- and myocardin (MYOCD)‑driven smooth muscle cell (SMC)-restricted gene expression, a process that aids in the differentiation of SMCs; and 2) whether G6PD-mediated metabolic reprogramming contributes to the pathogenesis of vascular diseases in metabolic syndrome (MetS). Inhibition of G6PD activity increased (>30%) expression of SMC-restricted genes and concurrently decreased (40%) the growth of human and rat SMCs ex vivo. Expression of SMC-restricted genes decreased ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 8, 2021 Category: Physiology Authors: Dhagia V, Kitagawa A, Jacob C, Zheng C, D'Alessandro A, Edwards JG, Rocic P, Gupte R, Gupte SA Tags: Am J Physiol Heart Circ Physiol Source Type: research

microRNA-30a-5p silencing polarizes macrophages towards M2 phenotype to alleviate cardiac injury following viral myocarditis by targeting SOCS1.
Abstract Viral myocarditis (VMC) is a life-threatening disease characterized by severe cardiac inflammation generally caused by coxsackievirus B3 (CVB3) infection. Several microRNAs (miRNAs or miRs) are known to play crucial roles in the pathogenesis of VMC. The study aims to decipher the role of miR-30a-5p in the underlying mechanisms of VMC pathogenesis. We first quantified miR-30a-5p expression in a CVB3-induced mouse VMC model. The physiological characteristics of mouse cardiac tissues were then detected by HE and Picrosirius red staining. We established the correlation between miR-30a-5p and SOCS1 using dual ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 8, 2021 Category: Physiology Authors: Zhang Y, Cai S, Ding X, Lu C, Wu R, Wu H, Shang Y, Pang M Tags: Am J Physiol Heart Circ Physiol Source Type: research

Differential negative effects of acute exhaustive swim exercise on the right ventricle is associated with disproportionate hemodynamic loading.
Abstract Acute exhaustive endurance exercise can differentially impact the right ventricle (RV) versus the left (LV). However, the hemodynamic basis for these differences and its impact on post-exercise recovery remains unclear. Therefore, we assessed cardiac structure and function along with hemodynamic properties of mice subjected to single bouts (216±8min) of exhaustive swimming (ES). One-hour after ES, LVs displayed mild diastolic impairment compared to sedentary (SED) mice. Following dobutamine administration to assess functional reserve, diastolic and systolic function were slightly impaired. Twenty-f...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 8, 2021 Category: Physiology Authors: Lakin R, Debi R, Yang S, Polidovitch N, Goodman JM, Backx PH Tags: Am J Physiol Heart Circ Physiol Source Type: research

Hypoxia-induced inhibition of mTORC1 activity in the developing lung: a possible mechanism for the developmental programming of pulmonary hypertension.
Abstract Perinatal hypoxia induces permanent structural and functional changes in the lung and its pulmonary circulation that are associated with the development of pulmonary hypertension (PH) in later life. The mechanistic target of the rapamycin (mTOR) pathway is vital for fetal lung development and implicated in hypoxia-associated PH, yet its involvement in the developmental programming of PH remains unclear. Pregnant C57/BL6 dams were placed in hyperbaric (760 mmHg) or hypobaric chambers during gestation (505 mmHg, day 15 through postnatal day 4) or adulthood (420 mmHg, postnatal day 21 through 8wks). Pulmonar...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 8, 2021 Category: Physiology Authors: Mundo W, Wolfson G, Moore LG, Houck JA, Park D, Julian CG Tags: Am J Physiol Heart Circ Physiol Source Type: research

Regular Aerobic Exercise Counteracts Endothelial Vasomotor Dysfunction Associated With Insufficient Sleep.
Abstract Insufficient sleep is associated with endothelial vasomotor dysfunction and increased cardiovascular risk. Regular aerobic exercise is an effective lifestyle strategy for improving endothelial function and, in turn, reducing cardiovascular risk. We tested the hypotheses that regular aerobic exercise would: 1) improve endothelial vasodilation; and 2) decrease ET-1-mediated vasoconstrictor tone in middle-aged adults who chronically sleep
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 8, 2021 Category: Physiology Authors: Stockelman KA, Bain AR, Dow CA, Diehl KJ, Greiner JJ, Stauffer BL, DeSouza CA Tags: Am J Physiol Heart Circ Physiol Source Type: research

Caveolin-3 is required for regulation of transient outward potassium current by angiotensin II in mouse atrial myocytes.
Abstract Angiotensin II (AngII) is a key mediator of the renin-angiotensin system and plays an important role in the regulation of cardiac electrophysiology by affecting various cardiac ion currents, including transient outward potassium current Ito. AngII receptors and molecular components of Ito, Kv4.2 and Kv4.3 channels, have been linked to caveolae structures. However, their functional interaction as well as the importance of such proximity within 50-100nm caveolar nanodomains, remain unknown. To address this, we studied the mechanisms of Ito regulation by AngII in atrial myocytes of wild type (WT) and cardiac...
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 8, 2021 Category: Physiology Authors: Tyan L, Turner D, Komp KR, Medvedev RY, Lim E, Glukhov AV Tags: Am J Physiol Heart Circ Physiol Source Type: research

Residential Proximity to Greenness Mitigates the Hemodynamic Effects of Ambient Air Pollution.
CONCLUSIONS: Residential proximity to greenness is associated with lower values of arterial stiffness. Residential greenness may mitigate the adverse effects of PM2.5 and ozone on arterial stiffness. PMID: 33416460 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - January 8, 2021 Category: Physiology Authors: Riggs DW, Yeager R, Conklin DJ, DeJarnett N, Keith RJ, DeFilippis AP, Rai SN, Bhatnagar A Tags: Am J Physiol Heart Circ Physiol Source Type: research

Diet alters age-related remodeling of aortic collagen in mice susceptible to atherosclerosis.
We examined two factors that can alter this balance, endothelial dysfunction and reduced smooth muscle cell (SMC) contractility. Collagen fiber organization was visualized by second-harmonic generation microscopy in aortic adventitia of apolipoprotein E (apoE) knockout (KO) mice at 6 wk and 6 mo of age on a chow diet and at 7.5 mo of age on a Western diet (WD), using image analysis to yield mean fiber orientation. Adventitial collagen fibers became significantly more longitudinally oriented with aging in apoE knockout mice on chow diet. Conversely, fibers became more circumferentially oriented with agi...
Source: American Journal of Physiology. Heart and Circulatory Physiology - December 31, 2020 Category: Physiology Authors: Watson SR, Cooper KM, Liu P, Gharraee N, Du L, Han SM, Peña EA, Sutton MA, Eberth JF, Lessner SM Tags: Am J Physiol Heart Circ Physiol Source Type: research

Hemodynamic Function of the Right Ventricular-Pulmonary Vascular-Left Atrial Unit: Normal Responses to Exercise in Healthy Adults.
Abstract With each heartbeat, the right ventricle (RV) inputs blood into the pulmonary vascular (PV) compartment which conducts blood through the lungs at low pressure and concurrently fills the left atrium (LA) for output to the systemic circulation. This overall hemodynamic function of the integrated RV-PV-LA unit is determined by complex interactions between the components that vary over the cardiac cycle but are often assessed in terms of mean pressure and flow. Exercise challenges these hemodynamic interactions as cardiac filling increases, stroke volume augments, and cycle length decreases, with PV pressures...
Source: American Journal of Physiology. Heart and Circulatory Physiology - December 24, 2020 Category: Physiology Authors: Wright SP, Dawkins TG, Eves ND, Shave RE, Tedford R, Mak S Tags: Am J Physiol Heart Circ Physiol Source Type: research

Importance of β2AR elevation for re-endothelialization capacity mediated by late endothelial progenitor cells in hypertensive patients.
Importance of β2AR elevation for re-endothelialization capacity mediated by late endothelial progenitor cells in hypertensive patients. Am J Physiol Heart Circ Physiol. 2020 Dec 24;: Authors: Hu Q, Guo Y, Zhang T, Feng J, Wang J, Dong X, Chen Y, Nie R, Feng Z, Huang Y, Deng M, Ke X Abstract Dysfunction of late endothelial progenitor cells (EPCs) has been suggested to be associated with hypertension. β2 adrenergic receptor (β2AR) is a novel and key target for EPCs homing. Here, we proposed that attenuated β2AR signaling contributes to EPCs dysfunction, whereas enhanced β2AR sig...
Source: American Journal of Physiology. Heart and Circulatory Physiology - December 24, 2020 Category: Physiology Authors: Hu Q, Guo Y, Zhang T, Feng J, Wang J, Dong X, Chen Y, Nie R, Feng Z, Huang Y, Deng M, Ke X Tags: Am J Physiol Heart Circ Physiol Source Type: research

Gpr43 regulates sodium butyrate-induced angiogenesis and matrix remodeling.
GPR43 REGULATES SODIUM BUTYRATE-INDUCED ANGIOGENESIS AND MATRIX REMODELING. Am J Physiol Heart Circ Physiol. 2020 Dec 24;: Authors: Castro PR, Bittencourt LFF, Larochelle S, Andrade SP, Mackay CR, Slevin MA, Moulin VJ, Barcelos LS Abstract Butyrate is a short-chain fatty acid (SCFA) derived from microbiota and is involved in a range of cell processes in a concentration-dependent manner. Low concentrations of sodium butyrate (NaBu) was shown to be proangiogenic. However, the mechanisms associated with these effects are not yet fully known. Here, we investigated the contribution of the SCFA receptor GPR...
Source: American Journal of Physiology. Heart and Circulatory Physiology - December 24, 2020 Category: Physiology Authors: Castro PR, Bittencourt LFF, Larochelle S, Andrade SP, Mackay CR, Slevin MA, Moulin VJ, Barcelos LS Tags: Am J Physiol Heart Circ Physiol Source Type: research