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Using heat as a therapeutic tool for the aging vascular tree
(Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - April 7, 2017 Category: Cardiology Authors: McGinn, R., Poirier, M. P., Kenny, G. P. Tags: PERSPECTIVES Source Type: research

Influence of sex on microvascular and macrovascular responses to prolonged sitting
Increased daily sitting time is associated with greater cardiovascular risk, and, on average, women are more sedentary than men. Recent reports have demonstrated that prolonged sitting reduces lower leg microvascular (reactive hyperemia) and macrovascular [flow-mediated dilation (FMD)] vasodilator function. However, these studies have predominately included men, and the effects of sitting in young women are largely unexplored. This becomes important given known sex differences in vascular function. Thus, herein, we assessed popliteal artery reactive hyperemia and FMD before and after a 3-h sitting period in healthy young w...
Source: AJP: Heart and Circulatory Physiology - April 1, 2017 Category: Cardiology Authors: Vranish, J. R., Young, B. E., Kaur, J., Patik, J. C., Padilla, J., Fadel, P. J. Tags: RAPID REPORT Source Type: research

NFAT regulation of cystathionine {gamma}-lyase expression in endothelial cells is impaired in rats exposed to intermittent hypoxia
This study identifies the calcium-regulated transcription factor nuclear factor of activated T cells as a novel regulator of cystathionine -lyase (CSE). This pathway is basally active in mesenteric artery endothelial cells, but, after exposure to intermittent hypoxia to mimic sleep apnea, nuclear factor of activated T cells c3 nuclear translocation and CSE expression are decreased, concomitant with decreased CSE-dependent vasodilation. (Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - April 1, 2017 Category: Cardiology Authors: Gonzalez Bosc, L. V., Osmond, J. M., Giermakowska, W. K., Pace, C. E., Riggs, J. L., Jackson-Weaver, O., Kanagy, N. L. Tags: RESEARCH ARTICLE Source Type: research

Atheroprotective vaccination with MHC-II-restricted ApoB peptides induces peritoneal IL-10-producing CD4 T cells
Although immunization with major histocompatibility complex (MHC) class II-restricted apolipoprotein B (ApoB) peptides has been shown to be atheroprotective, the mechanism is unclear. Here, we investigated CD4+ T cell populations in immunized atherosclerotic mice. Peptides (16-mers) from mouse ApoB, the core protein of low-density lipoprotein (LDL), were screened for binding to I-Ab by computer prediction and confirmed by radiolabeled peptide competition. Three new peptides, P101 (FGKQGFFPDSVNKALY, 5.5 nM IC50), P102 (TLYALSHAVNSYFDVD, 6.8 nM), and P103 (LYYKEDKTSLSASAAS, 95 nM), were tested in an atherosclerosis model (Ap...
Source: AJP: Heart and Circulatory Physiology - April 1, 2017 Category: Cardiology Authors: Kimura, T., Tse, K., McArdle, S., Gerhardt, T., Miller, J., Mikulski, Z., Sidney, J., Sette, A., Wolf, D., Ley, K. Tags: RESEARCH ARTICLE Source Type: research

Cardiac Med1 deletion promotes early lethality, cardiac remodeling, and transcriptional reprogramming
The mediator complex, a multisubunit nuclear complex, plays an integral role in regulating gene expression by acting as a bridge between transcription factors and RNA polymerase II. Genetic deletion of mediator subunit 1 (Med1) results in embryonic lethality, due in large part to impaired cardiac development. We first established that Med1 is dynamically expressed in cardiac development and disease, with marked upregulation of Med1 in both human and murine failing hearts. To determine if Med1 deficiency protects against cardiac stress, we generated two cardiac-specific Med1 knockout mouse models in which Med1 is conditiona...
Source: AJP: Heart and Circulatory Physiology - April 1, 2017 Category: Cardiology Authors: Spitler, K. M., Ponce, J. M., Oudit, G. Y., Hall, D. D., Grueter, C. E. Tags: RESEARCH ARTICLE Source Type: research

Blockade of CaMKII depresses conduction preferentially in the right ventricular outflow tract and promotes ischemic ventricular fibrillation in the rabbit heart
Calcium/calmodulin-dependent protein kinase II (CaMKII) regulates the principle ion channels mediating cardiac excitability and conduction, but how this regulation translates to the normal and ischemic heart remains unknown. Diverging results on CaMKII regulation of Na+ channels further prevent predicting how CaMKII activity regulates excitability and conduction in the intact heart. To address this deficiency, we tested the effects of the CaMKII blocker KN93 (1 and 2.75 μM) and its inactive analog KN92 (2.75 μM) on conduction and excitability in the left (LV) and right (RV) ventricles of rabbit hearts during normal p...
Source: AJP: Heart and Circulatory Physiology - April 1, 2017 Category: Cardiology Authors: Warren, M., Sciuto, K. J., Taylor, T. G., Garg, V., Torres, N. S., Shibayama, J., Spitzer, K. W., Zaitsev, A. V. Tags: RESEARCH ARTICLE Source Type: research

Cardiovascular function in male and female JCR:LA-cp rats: effect of high-fat/high-sucrose diet
Thirty percent of the world population is diagnosed with metabolic syndrome. High-fat/high-sucrose (HF/HS) diet (Western diet) correlates with metabolic syndrome prevalence. We characterized effects of the HF/HS diet on vascular (arterial stiffness, vasoreactivity, and coronary collateral development) and cardiac (echocardiography) function, oxidative stress, and inflammation in a rat model of metabolic syndrome (JCR rats). Furthermore, we determined whether male versus female animals were affected differentially by the Western diet. Cardiovascular function in JCR male rats was impaired versus normal Sprague-Dawley (SD) ra...
Source: AJP: Heart and Circulatory Physiology - April 1, 2017 Category: Cardiology Authors: Hunter, I., Soler, A., Joseph, G., Hutcheson, B., Bradford, C., Zhang, F. F., Potter, B., Proctor, S., Rocic, P. Tags: RESEARCH ARTICLE Source Type: research

A systems genetics approach identifies Trp53inp2 as a link between cardiomyocyte glucose utilization and hypertrophic response
Cardiac failure has been widely associated with an increase in glucose utilization. The aim of our study was to identify factors that mechanistically bridge this link between hyperglycemia and heart failure. Here, we screened the Hybrid Mouse Diversity Panel (HMDP) for substrate-specific cardiomyocyte candidates based on heart transcriptional profile and circulating nutrients. Next, we utilized an in vitro model of rat cardiomyocytes to demonstrate that the gene expression changes were in direct response to substrate abundance. After overlaying candidates of interest with a separate HMDP study evaluating isoproterenol-indu...
Source: AJP: Heart and Circulatory Physiology - April 1, 2017 Category: Cardiology Authors: Seldin, M. M., Kim, E. D., Romay, M. C., Li, S., Rau, C. D., Wang, J. J., Krishnan, K. C., Wang, Y., Deb, A., Lusis, A. J. Tags: RESEARCH ARTICLE Source Type: research

Right ventricular metabolism during venoarterial extracorporeal membrane oxygenation in immature swine heart in vivo
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides hemodynamic rescue for patients encountering right or left ventricular (RV or LV) decompensation, particularly after surgery for congenital heart defects. ECMO, supported metabolically by parenteral nutrition, provides reductions in myocardial work and energy demand and, therefore, enhances functional recovery. The RV must often assume systemic ventricular pressures and function on weaning from VA-ECMO. However the substrate utilization responses of the RV to VA-ECMO or stimulation are unknown. We determined RV and LV substrate utilization response to VA-E...
Source: AJP: Heart and Circulatory Physiology - April 1, 2017 Category: Cardiology Authors: Kajimoto, M., Ledee, D. R., Isern, N. G., Portman, M. A. Tags: RESEARCH ARTICLE Source Type: research

Cystathionine {gamma}-lyase protects vascular endothelium: a role for inhibition of histone deacetylase 6
Endothelial cystathionine -lyase (CSE) contributes to cardiovascular homeostasis, mainly through production of H2S. However, the molecular mechanisms that control CSE gene expression in the endothelium during cardiovascular diseases are unclear. The aim of the current study is to determine the role of specific histone deacetylases (HDACs) in the regulation of endothelial CSE. Reduced CSE mRNA expression and protein abundance were observed in human aortic endothelial cells (HAEC) exposed to oxidized LDL (OxLDL) and in aortas from atherogenic apolipoprotein E knockout (ApoE–/–) mice fed a high-fat diet compared w...
Source: AJP: Heart and Circulatory Physiology - April 1, 2017 Category: Cardiology Authors: Leucker, T. M., Nomura, Y., Kim, J. H., Bhatta, A., Wang, V., Wecker, A., Jandu, S., Santhanam, L., Berkowitz, D., Romer, L., Pandey, D. Tags: RESEARCH ARTICLE Source Type: research

The history of the microsphere method for measuring blood flows with special reference to myocardial blood flow: a personal memoir
We use many types of equipment and technologies to make our measurements but give little thought to how they developed. Evolution was once described as a series of recoils from blind alleys, and this is exemplified by the gradual development of the microsphere method of measuring blood flows. The microsphere method is one of the most frequently used methods for measuring blood flow to organs and portions of organs. The method can measure myocardial blood flow with reasonable accuracy (within 10%) down to samples weighing >50 mg but probably will not do so for samples weighing 1–10 mg. Microspheres with diameters f...
Source: AJP: Heart and Circulatory Physiology - April 1, 2017 Category: Cardiology Authors: Hoffman, J. I. E. Tags: HISTORICAL ARTICLE Source Type: research

Evidence for hysteresis in the cerebral pressure-flow relationship in healthy men
The cerebrovasculature is more efficient at compensating for pharmacologically induced transient hypertension versus transient hypotension. Whether this phenomenon exists during nonpharmacologically induced hypertension and hypotension is currently unknown. We compared the percent change in mean velocity in the middle cerebral artery (MCAvmean) per percent change in mean arterial pressure (MAP) (%MCAVmean/%MAP) during transient hypertension and hypotension induced during squat-stand maneuvers performed at 0.05 Hz (20-s cycles) and 0.10 Hz (10-s cycles) in 58 male volunteers. %MCAvmean/%MAP was attenuated by 25% (P = 0.03, ...
Source: AJP: Heart and Circulatory Physiology - April 1, 2017 Category: Cardiology Authors: Brassard, P., Ferland-Dutil, H., Smirl, J. D., Paquette, M., Le Blanc, O., Malenfant, S., Ainslie, P. N. Tags: RAPID REPORT Source Type: research

Why septal motion is a marker of right ventricular failure in pulmonary arterial hypertension: mechanistic analysis using a computer model
In conclusion, dyssynchrony in ventricular relaxation causes RLSM in PAH. Onset of RLSM in patients with PAH appears to indicate a worsening in RV function and hence can be used as a sign of RV failure. However, altered RLSM does not necessarily imply an altered RV afterload, but it can also indicate altered interplay of RV and LV contractile function. Reduction of RLSM can result from either improved RV function or a deterioration of LV function. NEW & NOTEWORTHY A novel approach describes the mechanism underlying abnormal septal dynamics in pulmonary arterial hypertension. Change in motion is not uniquely induced by ...
Source: AJP: Heart and Circulatory Physiology - April 1, 2017 Category: Cardiology Authors: Palau-Caballero, G., Walmsley, J., Van Empel, V., Lumens, J., Delhaas, T. Tags: RESEARCH ARTICLE Source Type: research

Peroxisome proliferator-activated receptor-{alpha} expression induces alterations in cardiac myofilaments in a pressure-overload model of hypertrophy
In this study we compared the function of skinned fiber bundles from transgenic (Tg) mice that overexpress a relatively low level of the peroxisome proliferator-activated receptor α (PPARα), and nontransgenic (NTg) littermates. The mice (NTg-T and Tg-T) were stressed by transverse aortic constriction (TAC) and compared with shams (NTg-S and Tg-S). There was an approximate 4-fold increase in PPARα expression in Tg-S compared with NTg-S, but Tg-T hearts showed the same PPARα expression as NTg-T. Expression of PPARα did not alter the hypertrophic response to TAC but did reduce ejection fraction (...
Source: AJP: Heart and Circulatory Physiology - April 1, 2017 Category: Cardiology Authors: Karam, C. N., Warren, C. M., Henze, M., Banke, N. H., Lewandowski, E. D., Solaro, R. J. Tags: RESEARCH ARTICLE Source Type: research

Oscillatory lower body negative pressure impairs working memory task-related functional hyperemia in healthy volunteers
Neurovascular coupling (NVC) describes the link between an increase in task-related neural activity and increased cerebral blood flow denoted "functional hyperemia." We previously showed induced cerebral blood flow oscillations suppressed functional hyperemia; conversely functional hyperemia also suppressed cerebral blood flow oscillations. We used lower body negative pressure (OLBNP) oscillations to force oscillations in middle cerebral artery cerebral blood flow velocity (CBFv). Here, we used N-back testing, an intellectual memory challenge as a neural activation task, to test the hypothesis that OLBNP-induced oscillator...
Source: AJP: Heart and Circulatory Physiology - April 1, 2017 Category: Cardiology Authors: Merchant, S., Medow, M. S., Visintainer, P., Terilli, C., Stewart, J. M. Tags: RESEARCH ARTICLE Source Type: research