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American Journal of Physiology. Heart and Circulatory Physiology

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https://www.readbyqxmd.com/read/28314764/b-cells-and-atherosclerosis
#1
Prasad Srikakulapu, Coleen McNamara
B cells have emerged as important immune cells in cardiovascular disease. Initial studies suggested that B cells protect against atherosclerosis development. However, subsequent studies demonstrating aggravation of atherosclerosis by B2 cells shed light on the subset-dependent effects of B cells. Here we review the literature that has led to our current understanding of B cell regulation of atherosclerosis, touching on the importance of subsets, local regulation, human translation and therapeutic potential.
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28314763/endothelial-dysfunction-inhibits-the-ability-of-haptoglobin-to-prevent-hemoglobin-induced-hypertension
#2
Jan A Graw, Binglan Yu, Emanuele Rezoagli, H Shaw Warren, Emmanuel S Buys, Donald B Bloch, Warren M Zapol
BACKGROUND: Intravascular hemolysis produces injury in a variety of human diseases including hemoglobinopathies, malaria, and sepsis. The adverse effects of increased plasma hemoglobin are partly mediated by depletion of nitric oxide (NO) and result in vasoconstriction. Circulating plasma proteins haptoglobin and hemopexin scavenge extracellular hemoglobin and cell-free heme, respectively. METHODS: The ability of human haptoglobin or hemopexin to inhibit the adverse effects of NO-scavenging by circulating murine hemoglobin was tested in C57Bl/6 mice...
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28314762/cerebral-microhemorrhages-mechanisms-consequences-and-prevention
#3
Zoltan I Ungvari, Stefano Tarantini, Angelia C Kirkpatrick, Anna Csiszar, Calin I Prodan
The increasing prevalence of multifocal cerebral microhemorrhages (CMHs, also known as "cerebral microbleeds") is a significant, newly recognized problem in the aging population of the Western world. CMHs are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function, potentially contributing to cognitive decline, geriatric psychiatric syndromes and gait disorders. Clinical studies show that aging and hypertension significantly increase prevalence of CMHs...
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28314761/hypoxia-mediated-regulation-of-the-secretory-properties-of-mitral-valve-interstitial-cells
#4
Kareem Salhiyyah, Padmini Sarathchandra, Najma Latif, Magdi H Yacoub, Adrian H Chester
The sophisticated function of the mitral valve depends to a large extent on the extracellular matrix (ECM) and specific cellular components. These are tightly regulated by a repertoire of mechanical stimuli and biological pathways. One potentially important pathway is hypoxia. The purpose of this investigation is to determine the effect of hypoxia on the regulation of mitral valve interstitial cells (MVIC) with respect to the synthesis and secretion of extracellular matrix proteins. Hypoxia resulted in reduced production of total collagen and sulphated glycosaminoglycans (sGAG) in cultured porcine MVIC...
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28314760/loss-of-vegfb-and-its-signaling-in-the-diabetic-heart-is-associated-with-increased-cell-death-signaling
#5
Nathaniel Lal, Amy Pei-Ling Chiu, Fulong Wang, Dahai Zhang, Jocelyn Jia, Andrea Wan, Israel Vlodavsky, Bahira Hussein, Brian Rodrigues
VEGFB is highly expressed in metabolically active tissues, such as the heart and skeletal muscle, suggesting a function in maintaining oxidative metabolic and contractile function in these tissues. Multiple models of heart failure have indicated a significant drop in VEGFB. However, whether there is a role for decreased VEGFB in diabetic cardiomyopathy is currently unknown. Of the VEGFB located in cardiomyocytes, there is a substantial and readily releasable pool localized on the cell surface. The immediate response to high glucose and the secretion of endothelial heparanase is the release of this surface bound VEGFB, which triggers signaling pathways and gene expression to influence endothelial cell (autocrine action) and cardiomyocyte (paracrine effects) survival...
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28314759/guidelines-in-cardiovascular-research-a-first-for-the-american-journal-of-physiology-heart-and-circulatory-physiology
#6
Irving H Zucker
not applicable for editorial.
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28314758/immune-checkpoint-dysfunction-in-medium-and-large-vessel-vasculitis
#7
Ryu Watanabe, Hui Zhang, Gerald Berry, Jorg J Goronzy, Cornelia M Weyand
Giant cell arteritis (GCA) is a granulomatous vasculitis of the aorta and its medium-sized branch vessels. CD4 T-cells, macrophages and dendritic cells build granulomatous infiltrates that injure the vessel wall and elicit a maladaptive response-to-injury. Pathologic consequences include fragmentation of elastic membranes, destruction of the medial layer, microvascular neoangiogenesis, massive outgrowth of myofibroblasts, and lumen-occlusive intimal hyperplasia. Antigens have been suspected to drive the local activation of vasculitogenic CD4 T-cells, but recent data suggest a more generalized defect in the threshold setting of such T-cells, rendering them hyperreactive...
March 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28283551/a-novel-role-for-mir-133a-in-centrally-mediated-activation-of-the-renin-angiotensin-system-in-congestive-heart-failure
#8
Neeru M Sharma, Shyam Sundar Nandi, Hong Zheng, Paras K Mishra, Kaushik P Patel
Activated renin-angiotensin system (RAS) within the central nervous system has been implicated in sympathoexcitation during various disease conditions including congestive heart failure (CHF). In particular, activation of RAS in the paraventricular nucleus (PVN) of the hypothalamus has been recognized to augment sympathoexcitation in CHF. We observed a 2.6-fold increase in angiotensinogen (AGT) in the PVN of CHF. To elucidate the molecular mechanism for increased expression of AGT, we performed in silico analysis of 3'-untranslated region (3'UTR) of AGT and found potential binding site for microRNA-133a(miR-133a)...
March 10, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28283550/the-effects-of-%C3%AE-adrenergic-receptor-drugs-on-embryonic-ventricular-cell-proliferation-and-differentiation-and-their-impact-on-donor-cell-transplantation
#9
Tiam Feridooni, Adam Hotchkiss, Mark Baguma-Nibasheka, Feixiong Zhang, Brittney Allen, Sarita Chinni, Kishore B S Pasumarthi
The beta-adrenergic receptors (β-ARs) and catecholamines are present in rodents as early as embryonic day 10.5 (E10.5). However, it is not known whether β-AR signaling plays any role in proliferation and differentiation of ventricular cells in the embryonic heart. Here, we characterized the expression profiles of β-AR subtypes and established dose response curves for a nonselective β-AR agonist isoproterenol (ISO) in the developing mouse ventricular cells. Further, we investigated the effects of ISO on cell cycle activity and differentiation of cultured E11...
March 10, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28283549/mild-hypothermia-preserves-myocardial-conduction-during-ischemia-by-maintaining-gap-junction-intracellular-communication-and-sodium-channel-function
#10
Michelle Mj Nassal, Xiaoping Wan, Zack Dale, Isabelle Deschenes, Lance D Wilson, Joseph Stephen Piktel
BACKGROUND: Acute cardiac ischemia induces conduction velocity (CV) slowing and conduction block, promoting reentrant arrhythmias leading to sudden cardiac arrest (SCA). Previously, we found that mild hypothermia (MH, 32°C) attenuates ischemia-induced conduction block and CV slowing in a canine model of early global ischemia. Acute ischemia impairs cellular excitability and the GJ protein connexin 43 (Cx43). We hypothesized that MH prevented ischemia-induced conduction block and CV slowing by preserving GJ expression and localization...
March 10, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28283548/smooth-muscle-cell-specific-deletion-of-col15a1-unexpectedly-leads-to-impaired-development-of-advanced-atherosclerotic-lesions
#11
Brittany G Durgin, Olga A Cherepanova, Delphine Gomez, Themistoclis Karaoli, Gabriel F Alencar, Joshua T Butcher, Yu-Qing Zhou, Michelle P Bendeck, Brant E Isakson, Gary K Owens, Jessica J Connelly
Atherosclerotic plaque rupture with subsequent embolic events is a major cause of sudden death from myocardial infarction or stroke. Although smooth muscle cells (SMC) produce and respond to collagens in vitro, there is no direct evidence in vivo that SMC are a crucial source of collagens and that this impacts lesion development or fibrous cap formation. We sought to determine how conditional SMC specific knockout of collagen type XV (COL15A1) in SMC lineage tracing mice affects advanced lesion formation given: 1) we previously identified a Col15a1 sequence variant associated with age related atherosclerosis; 2) COL15A1 is a matrix organizer enhancing tissue structural integrity; and 3) siRNA mediated Col15a1 knockdown increased migration and decreased proliferation of cultured human SMC...
March 10, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28258058/impact-of-mild-orthostatic-stress-on-aortic-cerebral-hemodynamic-transmission-insight-from-the-frequency-domain
#12
Jun Sugawara, Tsubasa Tomoto, Tomoko Imai, Seiji Maeda, Shigehiko Ogoh
High cerebral pressure and flow fluctuations could be a risk for future cerebrovascular disease. This study aims to determine whether acute systemic vasoconstriction affects the dynamic pulsatile hemodynamic transmission from the aorta to the brain. We applied a stepwise lower body negative pressure (LBNP) (-10, -20, and -30 mmHg) in 15 young men to induce systemic vasoconstriction. To elucidate the dynamic relationship between the changes in aortic pressure (AoP, estimated from the radial arterial pressure waveforms) and the cerebral blood flow velocity (CBFV) at the middle cerebral artery (via a transcranial Doppler), frequency-domain analysis characterized the beat-to-beat slow oscillation (0...
March 3, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28258057/psoriasis-as-a-human-model-of-disease-to-study-inflammatory-atherogenesis
#13
Charlotte L Harrington, Amit K Dey, Raza Yunus, Aditya A Joshi, Nehal N Mehta
Inflammation is known to play a significant role in the process of atherogenesis and cardiovascular disease (CVD). Indeed, patients with chronic inflammatory diseases are at increased risk for cardiovascular events. The mechanisms linking chronic inflammation and CVD however remain poorly understood. Psoriasis, a chronic inflammatory skin disease associated with a greater risk of early cardiovascular events, provides a suitable human model to study the pathophysiology of inflammatory atherogenesis in humans...
March 3, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28235792/cardiovascular-consequences-of-the-inspiratory-muscle-metaboreflex-effects-of-age-and-sex
#14
Joshua R Smith, Andrew M Alexander, Shane M Hammer, Kaylin D Didier, Stephanie P Kurti, Ryan M Broxterman, Thomas J Barstow, Craig A Harms
We hypothesized that, compared to their younger counterparts, older men and women would exhibit greater 1) increases in mean arterial pressure (MAP) and limb vascular resistance (LVR) and 2) decreases in limb blood flow (Q̇L), but 3) no sex differences would be present in older adults. Sixteen young (8 men (YM), 8 women (YW); 18-24 yrs) and older (8 men (OM), 8 women (OW); 60-73 yrs) adults performed inspiratory resistive breathing tasks (IRBTs) at 2% and 65% of their maximal inspiratory pressure. During the IRBTs, breathing frequency was 20 breaths min-1 with a 50% duty cycle...
February 24, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28235791/high-throughput-screening-identifies-micrornas-that-target-nox2-and-improve-function-following-acute-myocardial-infarction
#15
Junyu Yang, Milton E Brown, Hanshuo Zhang, Mario Martinez, Zhihua Zhao, Srishti Bhutani, Shenyi Yin, David Trac, Jianzhong Jeff Xi, Michael E Davis
AIMS: Myocardial infarction (MI) is the most common cause of heart failure. Excessive production of reactive oxygen species plays a key role in the pathogenesis of cardiac remodeling after MI. NADPH with Nox2 as the catalytic subunit is a major source of superoxide production and expression is significantly increased in the infarcted myocardium, especially by infiltrating macrophages. While microRNAs (miRNAs) are potent regulators of gene expression, and play an important role in heart disease, there still lacks efficient ways to identify miRNAs that target important pathological genes for treating MI...
February 24, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28235790/short-term-regular-aerobic-exercise-reduces-oxidative-stress-produced-by-acute-high-intraluminal-pressure-in-the-adipose-microvasculature
#16
Austin T Robinson, Ibra S Fancher, Varadarajan Sudhahar, Jing Tan Bian, Marc Cook, Abeer M Mahmoud, Mohamed Ali, Masuko Ushio-Fukai, Michael D Brown, Tohru Fukai, Shane A Phillips
High blood pressure has been shown to elicit impaired dilation in the vasculature. The purpose of this investigation was to elucidate the mechanisms through which high pressure may elicit vascular dysfunction, and determine the mechanisms through which regular aerobic exercise protects arteries against high pressure. METHODS: Male C57Bl6 mice were subjected to two weeks of voluntary running (~ 6km/day) for comparison to sedentary controls. Hind limb adipose resistance arteries were dissected from mice for measurement of flow-induced dilation (FID; with or without high intraluminal pressure exposure); or protein expression of NADPH oxidase II (NOX II) and superoxide dismutase (SOD)...
February 24, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28235789/erbb-signaling-attenuates-pro-inflammatory-activation-of-non-classical-monocytes
#17
Sergey Ryzhov, Anton Matafonov, Cristi L Galindo, Qinkun Zhang, Truc-Linh Tran, Daniel P Lenihan, Carrie Geisberg Lenneman, Igor Feoktistov, Douglas B Sawyer
Immune activation in chronic systolic heart failure (HF) correlates with disease severity and prognosis. Recombinant neuregulin-1 (NRG-1) is being developed as a possible therapy for HF based on activation of ERBB receptors in cardiac cells. Work in animal models of HF led us to hypothesize that there may be direct effects of NRG-1 on immune system activation and inflammation. We investigated the expression of ERBB receptors and the effect of the recombinant NRG-1 isoform glial growth factor 2 (GGF2) in subpopulations of peripheral blood mononuclear cells in subjects with HF...
February 24, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28235788/systems-genetics-approach-identifies-trp53inp2-as-a-link-between-cardiomyocyte-glucose-utilization-and-hypertrophic-response
#18
Marcus M Seldin, Eric D Kim, Milagros C Romay, Shen Li, Christoph D Rau, Jessica J Wang, Karthickeyan Chella Krishnan, Yibin Wang, Arjun Deb, Aldons J Lusis
Cardiac failure has been widely associated with an increased glucose utilization. The aim of our present study was to identify factors which 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...
February 24, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28213406/mitochondria-regulated-formation-of-endothelial-extracellular-vesicles-shifts-the-mediator-of-flow-induced-vasodilation
#19
Julie K Freed, Matthew J Durand, Brian Robert Hoffmann, John C Densmore, Andrew S Greene, David D Gutterman
In order to examine the effect of endothelial-derived extracellular vesicles (eEVs) on the mechanism of flow-induced dilation (FID) composition, formation, and functional effects on the mechanism of FID were examined from two different eEV subtypes, one produced from ceramide, the other from plasminogen-activator inhibitor 1 (PAI-1). Using videomicroscopy, internal diameter changes in response to increases in flow were measured in human adipose resistance arteries acutely exposed (30min) to eEVs derived from cultured endothelial cells exposed to ceramide or PAI-1...
February 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28213405/inhibition-of-the-mtor-pathway-in-abdominal-aortic-aneurysm-implication-of-smooth-muscle-cell-contractile-phenotype-inflammation-and-aneurysm-expansion
#20
Guangxin Li, Lingfeng Qin, Lei Wang, Xuan Li, Alexander W Caulk, Jian Zhang, Pei-Yu Chen, Shijie Xin
The development of effective pharmacological treatment of abdominal aortic aneurysm (AAA) potentially offers great benefit to patients with pre-aneurysmal aortic dilation by slowing the expansion of aneurysms and reducing the need for surgery. To date, therapeutic targets for slowing aortic dilation have had low efficacy. Thus, in this study, we aim to elucidate possible mechanisms driving aneurysm progression in order to identify potential targets for pharmacological intervention. We demonstrate that mTOR signaling is over activated in aortic smooth muscle cells (SMCs) which contributes to murine AAA...
February 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
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