Persistent insulin signaling coupled with restricted PI3K activation causes insulin-induced vasoconstriction.
Abstract Insulin modulates vasomotor tone through vasodilator and vasoconstrictor signaling pathways. The purpose of the present work was to determine whether insulin-stimulated vasoconstriction is a pathophysiological phenomenon that can result from a combination of persistent insulin signaling, suppressed PI3K activation and an ensuing relative increase in MAPK/endothelin-1 (ET-1) activity. First, we examined previously published work from our group where we assessed changes in lower limb blood flow in response to an oral glucose tolerance test (endogenous insulin stimulation) in lean and obese subjects. The new...
Source: American Journal of Physiology. Heart and Circulatory Physiology - October 10, 2019 Category: Physiology Authors: Olver TD, Grunewald ZI, Ghiarone T, Restaino RM, Sales ARK, Park LK, Thorne PK, Ganga RR, Emter CA, Lemon PW, Shoemaker JK, Manrique-Acevedo C, Martinez-Lemus LA, Padilla J Tags: Am J Physiol Heart Circ Physiol Source Type: research

BDNF Downregulates Adrenergic β-Receptor-Mediated Hypotensive Mechanisms in the Paraventricular Nucleus of the Hypothalamus.
BDNF Downregulates Adrenergic β-Receptor-Mediated Hypotensive Mechanisms in the Paraventricular Nucleus of the Hypothalamus. Am J Physiol Heart Circ Physiol. 2019 Oct 11;: Authors: Thorsdottir D, Cruickshank NC, Einwag Z, Hennig GW, Erdos B Abstract Brain-derived neurotrophic factor (BDNF) is upregulated in the paraventricular nucleus of the hypothalamus (PVN) in response to hypertensive stimuli such as stress and hyperosmolality, and BDNF, acting in the PVN plays a key role in elevating sympathetic activity and blood pressure. However, downstream mechanisms mediating these effects remain unclear...
Source: American Journal of Physiology. Heart and Circulatory Physiology - October 10, 2019 Category: Physiology Authors: Thorsdottir D, Cruickshank NC, Einwag Z, Hennig GW, Erdos B Tags: Am J Physiol Heart Circ Physiol Source Type: research

Ventricular vortex loss analysis due to various tricuspid valve repair techniques: an ex vivo study.
In this study, the hemodynamics of the right ventricle (RV) after (i) clover edge-to-edge tricuspid repair and (ii) double orifice tricuspid repair was evaluated in three right heart models using an ex vivo pulsatile platform emulating severe FTR with the aid of stereoscopic particle image velocimetry. Although all repairs substantially reduced tricuspid regurgitant area, they resulted in more than 50% reduction in diastolic tricuspid valve (TV) opening area. Splitting the TV orifice into multiple smaller orifices by both repairs eliminated the ring-shaped vortical structure inside the RV observed in FTR cases. Post-repair...
Source: American Journal of Physiology. Heart and Circulatory Physiology - October 10, 2019 Category: Physiology Authors: Nguyen YN, Tay ELW, Kabinejadian F, Ong CW, Ismail M, Leo HL Tags: Am J Physiol Heart Circ Physiol Source Type: research

A Critical Appraisal of the Tafazzin Knockdown Mouse Model of Barth Syndrome: What Have We Learned About Pathogenesis and Potential Treatments?
Abstract Pediatric heart failure remains poorly understood, distinct in many aspects from adult heart failure. Limited data point to roles of altered mitochondrial functioning and in particular, changes in mitochondrial lipids, especially cardiolipin. Barth syndrome is a mitochondrial disorder caused by tafazzin mutations that lead to abnormal cardiolipin profiles. Patients are afflicted by cardiomyopathy, skeletal myopathy, neutropenia, and growth delay. A mouse model of Barth syndrome was developed a decade ago, which relies on a doxycycline-inducible shRNA to knock down expression of tafazzin mRNA ("TAZKD&...
Source: American Journal of Physiology. Heart and Circulatory Physiology - October 10, 2019 Category: Physiology Authors: Ren M, Miller PC, Schlame M, Phoon CKL Tags: Am J Physiol Heart Circ Physiol Source Type: research

SUMO2 regulates vascular endothelial function and oxidative stress in mice.
Abstract SUMOylation is a post-translational modification of lysine residues. Modification of proteins by SUMO1, 2, and 3 can achieve varied, and often unique, physiological and pathological effects. We looked for SUMO2-specific effects on vascular endothelial function. SUMO2 expression was upregulated in the aortic endothelium of hypercholesterolemic LDLr-/- mice and was responsible for impairment of endothelium-dependent vasorelaxation in these mice. Moreover, overexpression of SUMO2 in aortas ex vivo, in cultured endothelial cells, and transgenically in the endothelium of mice increased vascular oxidative stres...
Source: American Journal of Physiology. Heart and Circulatory Physiology - October 3, 2019 Category: Physiology Authors: Kim YR, Jacobs JS, Li Q, Gaddam RR, Vikram A, Liu J, Kassan M, Irani K, Kumar S Tags: Am J Physiol Heart Circ Physiol Source Type: research

Salt restriction lowers blood pressure at rest and during exercise without altering peripheral hemodynamics in hypertensive individuals.
Abstract Dietary salt restriction is a well-established approach to lower blood pressure and reduce cardiovascular disease risk in hypertensive individuals. However, little is currently known regarding the effects of salt restriction on central and peripheral hemodynamic responses to exercise in those with hypertension. Therefore, this study sought to determine the impact of salt restriction on the central and peripheral hemodynamic responses to static-intermittent handgrip (HG) and dynamic single-leg knee extension (KE) exercise in patients with hypertension. Twenty-two patients (14M / 8F, 51 ± 10y, 173 &p...
Source: American Journal of Physiology. Heart and Circulatory Physiology - October 3, 2019 Category: Physiology Authors: Ratchford SM, Broxterman RM, La Salle DT, Kwon OS, Hopkins PN, Richardson RS, Trinity JD Tags: Am J Physiol Heart Circ Physiol Source Type: research

A 4D Flow MRI Evaluation of the Impact of Shear-Dependent Fluid Viscosity on in vitro Fontan Circulation Flow.
Abstract The Fontan procedure for univentricular heart defects creates a non-physiologic circulation where systemic venous blood drains directly into the pulmonary arteries, leading to multiorgan dysfunction secondary to chronic low-shear non-pulsatile pulmonary blood flow and central venous hypertension. Although blood viscosity increases exponentially in this low-shear environment, the role of shear-dependent ("non-Newtonian") blood viscosity in this pathophysiology is unclear. We studied 3D-printed Fontan models in an in vitro flow loop with a Philips 3T MRI scanner. A 4D flow phase-contrast sequence ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - October 3, 2019 Category: Physiology Authors: Cheng AL, Wee CP, Pahlevan NM, Wood JC Tags: Am J Physiol Heart Circ Physiol Source Type: research

Sodium, Hypertension, and the Gut: Does the Gut Microbiota Go Salty?
Abstract Recent evidence suggests the gut microbiota contributes to the pathogenesis of hypertension (HTN). The gut microbiota is a highly dynamic organ mediating numerous physiological functions, which can be influenced by external factors such as diet. In particular, a major modifiable risk factor for HTN is dietary sodium intake. Sodium consumption in the United States is significantly greater than recommended by the federal government and organizations such as the American Heart Association. Due to the emerging connection between the gut microbiota and HTN, the interaction between dietary sodium and gut microb...
Source: American Journal of Physiology. Heart and Circulatory Physiology - October 3, 2019 Category: Physiology Authors: Smiljanec K, Lennon SL Tags: Am J Physiol Heart Circ Physiol Source Type: research

A call to adopt a 'fit-for-purpose' approach to antibody validation for flow cytometry analyses of stem cell models and beyond.
Abstract Human pluripotent stem cell-derived cardiomyocytes (hPSC-CM) can be exploited as models for a wide range of research applications and numerous protocols for generating hPSC-CM have been described. However, it is currently not possible to direct differentiation to a single, homogeneous endpoint, and the resulting heterogeneity may be variable among laboratories, cell lines, and protocols. Consequently, the ability to assess phenotypic heterogeneity of the cell population is critical to the interpretation, repeatability, and reproduction of hPSC-CM studies. While flow cytometry is well-suited for this purpo...
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 26, 2019 Category: Physiology Authors: Waas M, Gundry RL Tags: Am J Physiol Heart Circ Physiol Source Type: research

High-Frequency Murine Ultrasound Provides Enhanced Metrics of BAPN-Induced AAA Growth.
In this study, we worked to evaluate additional distinguishing factors between growing and stable murine aneurysms toward the aim of eventually improving clinical rupture risk assessment. By utilizing a relatively new mouse model that combines surgical application of topical elastase to cause initial aortic expansion, and a lysyl oxidase inhibitor, β-aminopropionitrile (BAPN), in the drinking water, we were able to create large AAAs that expanded over 28 days. We further sought to develop and demonstrate applications of advanced imaging approaches, including four-dimensional ultrasound (4DUS), to evaluate alternative ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 26, 2019 Category: Physiology Authors: Romary DJ, Berman AG, Goergen CJ Tags: Am J Physiol Heart Circ Physiol Source Type: research

Gut microbiota regulates cardiac ischemic tolerance and aortic stiffness in obesity.
Abstract The gut microbiota has emerged as an important regulator of host physiology, with recent data suggesting a role in modulating cardiovascular health. The present study determined if gut microbial signatures could transfer cardiovascular risk phenotypes between lean and obese mice using cecal microbiota transplantation (CMT). Pooled cecal contents collected from obese leptin-deficient (Ob) mice or C57Bl/6j control (Con) mice were transplanted by oral gavage into cohorts of recipient Ob and Con mice maintained on identical low-fat diets for 8 weeks (n=9-11/group). Cardiovascular pathology was assessed as the...
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 26, 2019 Category: Physiology Authors: Battson ML, Lee DM, Li Puma LC, Ecton KE, Thomas KN, Febvre HP, Chicco AJ, Weir TL, Gentile CL Tags: Am J Physiol Heart Circ Physiol Source Type: research

On the importance of the non-uniform aortic stiffening in the hemodynamics of physiological ageing.
Abstract Mathematical models of the arterial tree constitute a valuable tool to investigate the hemodynamics of ageing and pathology. Rendering such models patient-specific could allow for the assessment of central hemodynamic variables of clinical interest. However, this task is challenging, particularly with respect to the tuning of the local area compliance that varies significantly along the arterial tree. Accordingly, in this study, we demonstrate the importance of taking into account the differential effects of ageing on the stiffness of central and peripheral arteries when simulating a person's hemodynamic ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 19, 2019 Category: Physiology Authors: Pagoulatou SZ, Bikia V, Trachet B, Papaioannou TG, Protogerou AD, Stergiopulos N Tags: Am J Physiol Heart Circ Physiol Source Type: research

Thoracic spinal cord neuromodulation obtunds dorsal root ganglion afferent neuronal transduction of the ischemic ventricle.
Abstract Background: Aberrant afferent signaling drives adverse remodeling of the cardiac nervous system in ischemic heart disease. The study objective was to determine whether thoracic spinal dorsal column stimulation (SCS) modulates cardiac afferent sensory transduction of the ischemic ventricle. Methods: In anesthetized canines (n=16), extracellular activity generated by 62 dorsal root ganglia soma (T1-T3), with verified myocardial ischemic (MI) sensitivity, were evaluated with and without 20 min pre-emptive SCS (T1-T3 spinal level; 50 Hz, 90% motor threshold). Transient MI was induced by 1 min coronary artery ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 19, 2019 Category: Physiology Authors: Salavatian S, Ardell SM, Hammer M, Gibbons DD, Armour JA, Ardell JL Tags: Am J Physiol Heart Circ Physiol Source Type: research

Gravin Gravitates Atherogenesis to Atheroprogression in the Obesogenic Setting.
PMID: 31518153 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 12, 2019 Category: Physiology Authors: Kain V, Halade GV Tags: Am J Physiol Heart Circ Physiol Source Type: research

PAPP-A and the IGF system in Atherosclerosis - What's Up, What's Down?
Abstract Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase with a well-established role in releasing bioactive insulin-like growth factor 1 (IGF1) from IGF binding protein 2, -4 and -5 by proteolytic processing of these. The IGF system has repeatedly been suggested to be involved in the pathology of atherosclerosis, and both PAPP-A and IGF1 are proposed biomarkers and therapeutic targets for this disease. Several experimental approaches based on atherosclerosis mouse models have been undertaken to obtain causative and mechanistic insight to the role of these molecules in atherogenesis. However,...
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 12, 2019 Category: Physiology Authors: Steffensen LB, Conover CA, Oxvig C Tags: Am J Physiol Heart Circ Physiol Source Type: research

Venous return and the physical connection between distribution of segmental pressures and volumes.
Conclusion: the (Pms - Pra)/F formulation was never about Pms physically driving venous return; it was about how intravascular volume distributes among compliant compartments in accordance with their flow-dependent distending pressures, arbitrarily expressed relative to Pra rather than arterial pressure. PMID: 31518160 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 12, 2019 Category: Physiology Authors: Brengelmann GL Tags: Am J Physiol Heart Circ Physiol Source Type: research

Impaired function of aorta and perivascular adipose tissue in IL-18-deficient mice.
Abstract Interleukin-18 (IL-18) is ubiquitously produced by both hematopoietic and non-hematopoietic cells, but the central biological role of IL-18 in non-hematopoietic cells has not been sufficiently elucidated. In the present study, we examined the thoracic aorta, including perivascular adipose tissue (PVAT) of the IL-18 knockout (KO) mice in terms of functional and histological aspects. IL-18KO mice exhibited significantly higher blood pressure compared with wild-type (WT) mice. Echocardiographic examination showed a thickened vascular wall and narrowed vascular diameter of the abdominal aorta. Examination b...
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 12, 2019 Category: Physiology Authors: Li W, Jin D, Takai S, Hayakawa T, Ogata J, Yamanishi K, Yamanishi H, Okamura H Tags: Am J Physiol Heart Circ Physiol Source Type: research

Thymine DNA Glycosylase (TDG) is a Key Regulator of CaMKII γ Expression and Vascular Smooth Muscle Phenotype.
This study indicates that CaMKIIg expression in VSM is regulated by cytosine methylation/demethylation and that TDG is an important determinant of this process and, more broadly, VSM phenotype switching and function. PMID: 31518169 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 12, 2019 Category: Physiology Authors: Liu Y, Sun LY, Singer DV, Ginnan R, Zhao W, Jourd'heuil FL, Jourd'heuil D, Long X, Singer HA Tags: Am J Physiol Heart Circ Physiol Source Type: research

Can Intestinal Microbiota and Circulating Microbial Products Contribute to Pulmonary Arterial Hypertension?
Abstract Pulmonary arterial hypertension (PAH) is a fatal disease with a median survival of only 5-7 years. PAH is characterized by remodeling of the pulmonary vasculature causing reduced pulmonary arterial compliance (PAC) and increased pulmonary vascular resistance (PVR), ultimately resulting in right ventricular failure and death. Better therapies for PAH will require a paradigm shift in our understanding of the early pathophysiology. PAC decreases before there is an increase in the PVR. Unfortunately, current treatment has little effect on PAC. The loss of compliance correlates with extracellular matrix remode...
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 5, 2019 Category: Physiology Authors: Thenappan T, Khoruts A, Chen Y, Weir EK Tags: Am J Physiol Heart Circ Physiol Source Type: research

Renal denervation improves sodium excretion in rats with chronic heart failure: Effects on expression of renal ENaC and AQP2.
Abstract Previously we have shown that increased expression of renal epithelial sodium channels (ENaC) may contribute to the renal sodium and water retention observed during chronic heart failure (CHF). The goal of this study was to examine whether renal denervation (RDN) changed the expressions of renal sodium transporters ENaC, sodium-hydrogen exchanger-3 proteins (NHE3), and water channel aquaporin 2 (AQP2) in rats with CHF. CHF was produced by left coronary artery ligation in rats. Four weeks after ligation surgery, surgical bilateral RDN were performed. The expression of ENaC, NHE3 and AQP2 in both renal cort...
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 5, 2019 Category: Physiology Authors: Zheng H, Liu X, Katsurada K, Patel KP Tags: Am J Physiol Heart Circ Physiol Source Type: research

Effects of prolonged type 2 diabetes on mitochondrial function in cerebral blood vessels.
In conclusion, prolonged dietary diabetes leads to stabilization, rather than deterioration of metabolic status in the cerebral circulation, despite continued overproduction of ROS. PMID: 31490734 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - September 5, 2019 Category: Physiology Authors: Merdzo I, Rutkai I, Sure VNLR, Katakam PVG, Busija DW Tags: Am J Physiol Heart Circ Physiol Source Type: research

Reconstitution of autophagy ameliorates vascular function and arterial stiffening in spontaneously hypertensive rats.
Abstract Insufficient autophagy has been proposed as a mechanism of cellular aging, as this leads to the accumulation of dysfunctional macromolecules and organelles. Premature vascular aging occurs in hypertension. In fact, many factors that contribute to the deterioration of vascular function as we age are accelerated in clinical and experimental hypertension. Previously, we have reported decreased autophagy in arteries from spontaneously hypertensive rats (SHR); however, the effects of restoring autophagic activity on blood pressure and vascular function are currently unknown. We hypothesized that reconstitution...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 29, 2019 Category: Physiology Authors: McCarthy CG, Wenceslau CF, Calmasini FB, Klee NS, Brands MW, Joe B, Webb RC Tags: Am J Physiol Heart Circ Physiol Source Type: research

The gut microbiome and atherosclerosis: current knowledge and clinical potential.
Abstract Cardiovascular disease (CVD) is the leading cause of death worldwide. The human body is populated by a diverse community of microbes, dominated by bacteria, but also including viruses and fungi. The largest and most complex of these communities is located in the gastrointestinal system and with their associated genome, are known as the gut microbiome. Gut microbiome perturbations and related dysbiosis have been implicated in the progression and pathogenesis of CVD, including atherosclerosis, hypertension and heart failure. Although there have been advances in the characterisation and analysis of the gut m...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 29, 2019 Category: Physiology Authors: Ahmad A, Dwivedi G, O'Gara F, Caparros-Martin J, Ward N Tags: Am J Physiol Heart Circ Physiol Source Type: research

Long non-coding RNA LINC00342 promotes growth of infantile hemangioma by sponging miR-3619-5p from HDGF.
Abstract Infantile hemangiomas (IH) are a type of benign vascular neoplasms, which may cause permanent scarring. Hemangioma-derived endothelial cells (HemECs) are commonly used as an in vitro model to study IH. Long non-coding RNA (lncRNA) is a type of RNA transcripts longer than 200 nucleotides which do not encode any protein. LINC00342 was discovered to regulate proliferation and apoptosis in non-small cell lung cancer. However, the role of LINC00342 in IH has never been reported before. Expressions of LINC00342 and miR-3619-5p were detected in proliferating versus normal skin tissues. Colony formation and CCK-8...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 29, 2019 Category: Physiology Authors: Liu Z, Kang Z, Dai Y, Zheng H, Wang Y Tags: Am J Physiol Heart Circ Physiol Source Type: research

Preeminent Role of the Cardiorenal Axis in the Antihypertensive Response to an Arteriovenous Fistula: An In Silico Analysis.
Abstract Percutaneous creation of a small central arteriovenous (AV) fistula is currently being evaluated for the treatment of uncontrolled hypertension (HT). Although the mechanisms that contribute to the antihypertensive effects of the fistula are unclear, investigators have speculated that chronic blood pressure (BP) lowering may be due to: 1) reduced total peripheral resistance (TPR), 2) increased secretion of atrial natriuretic peptide (ANP), and/or 3) suppression of renal sympathetic nerve activity (RSNA). We used an established integrative mathematical model of human physiology to investigate these possibil...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 29, 2019 Category: Physiology Authors: Clemmer JS, Pruett WA, Hester RL, Lohmeier TE Tags: Am J Physiol Heart Circ Physiol Source Type: research

Investigation of the mechanisms of cyclooxygenase-mediated mechanoreflex sensitization in a rat model of simulated peripheral artery disease.
Abstract Mechanical and metabolic stimuli within contracting skeletal muscles reflexly increase sympathetic nervous system activity and blood pressure. That reflex, termed the exercise pressor reflex, is exaggerated in peripheral artery disease (PAD) patients and in a rat PAD model with a chronically ligated femoral artery. The cyclooxygenase (COX) pathway contributes to the exaggerated pressor response during rhythmic skeletal muscle contractions in PAD patients but the specific mechanism(s) of the COX-mediated exaggeration is not known. In decerebrate, unanesthetized rats with a chronically ligated femoral arter...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 29, 2019 Category: Physiology Authors: Butenas ALE, Hopkins TD, Rollins KS, Felice KP, Copp SW Tags: Am J Physiol Heart Circ Physiol Source Type: research

c-Kit Suppresses Atherosclerosis in Hyperlipidemic Mice.
Abstract Atherosclerosis is the most common underlying cause of cardiovascular morbidity and mortality worldwide. c-Kit (CD117) is a member of the receptor tyrosine kinase family, which regulates differentiation, proliferation, and survival of multiple cell types. Recent studies have shown that c-Kit and its ligand stem cell factor (SCF) are present in arterial endothelial cells and smooth muscle cells (SMCs). The role of c-Kit in cardiovascular disease remains unclear. The aim of the current study is to determine the role of c-Kit in atherogenesis. For this purpose, atherosclerotic plaques were quantified in c-Ki...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 22, 2019 Category: Physiology Authors: Song L, Zigmond Z, Martinez L, Lassance-Soares RM, Macias AE, Velazquez OC, Liu ZJ, Salama A, Webster KA, Vazquez-Padron RI Tags: Am J Physiol Heart Circ Physiol Source Type: research

Inflammation in non-ischemic heart disease: initiation by cardiomyocyte CaMKII and NLRP3 inflammasome signaling.
Abstract There is substantial evidence that chronic heart failure in humans and in animal models is associated with inflammation. Ischemic interventions such as myocardial infarction (MI) lead to necrotic cell death and release of damage associated molecular patterns (DAMPs), factors that signal cell damage and induce expression of pro-inflammatory chemokines and cytokines. It has recently become evident that non-ischemic interventions are also associated with increases in inflammatory genes and immune cell accumulation in the heart and that these contribute to fibrosis and ventricular dysfunction. How pro-inflamm...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 22, 2019 Category: Physiology Authors: Suetomi T, Miyamoto S, Brown JH Tags: Am J Physiol Heart Circ Physiol Source Type: research

Cortical bone derived stem-cell therapy reduces apoptosis after myocardial infarction.
Abstract Ischemic heart diseases like myocardial infarction are the largest contributors to cardiovascular disease world-wide. The resulting cardiac cell death impairs function of the heart and can lead to heart failure and death. Reperfusion of the ischemic tissue is necessary but causes damage to the surrounding tissue by re-perfusion injury. Cortical bone stem cells (CBSCs) have been shown to increase pump function and decrease scar size in a large animal swine model of myocardial infarction (MI). To investigate the potential mechanism for these changes, we hypothesized that CBSCs were altering cardiac cell dea...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 22, 2019 Category: Physiology Authors: Hobby AR, Sharp Iii TE, Berretta RM, Borghetti G, Feldsott E, Mohsin S, Houser SR Tags: Am J Physiol Heart Circ Physiol Source Type: research

Absence of Gravin Mediated Signaling Inhibits Development of High Fat Diet-Induced Hyperlipidemia and Atherosclerosis.
Abstract Gravin, an A-kinase anchoring protein (AKAP), is known to play a role in regulating key processes that lead to inflammation and atherosclerosis development; namely, cell migration, proliferation, and apoptosis. We investigated the role of gravin in the development of high-fat-diet (HFD) induced atherosclerosis and hyperlipidemia. Five-week-old male wild-type (WT) and gravin-t/t mice were fed normal-diet (ND) or HFD for 16-weeks. Gravin-t/t mice showed significantly lower liver-to-body-weight ratio, cholesterol, triglyceride, and very low-density lipoprotein levels in serum as compared to WT mice on HFD. F...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 22, 2019 Category: Physiology Authors: Fan Q, Yin X, Rababa'h A, Diaz Diaz A, Wijaya CS, Singh S, Suryavanshi SV, Vo HH, Saeed M, Zhang Y, McConnell BK Tags: Am J Physiol Heart Circ Physiol Source Type: research

Global reach 2018: reduced flow-mediated dilation stimulated by sustained increases in shear stress in high-altitude excessive erythrocytosis.
GLOBAL REACH 2018: REDUCED FLOW-MEDIATED DILATION STIMULATED BY SUSTAINED INCREASES IN SHEAR STRESS IN HIGH-ALTITUDE EXCESSIVE ERYTHROCYTOSIS. Am J Physiol Heart Circ Physiol. 2019 Aug 23;: Authors: Tremblay JC, Coombs GB, Howe CA, Vizcardo-Galindo G, Figueroa-Mujica RJ, Bermudez D, Tymko MM, Villafuerte FC, Ainslie PN, Pyke KE Abstract Excessive erythrocytosis (EE; hemoglobin concentration [Hb] ≥21 g dl-1 in adult males) is a maladaptive high-altitude pathology associated with increased cardiovascular risk and reduced reactive hyperemia flow-mediated dilation; however, whether a similar impairment...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 22, 2019 Category: Physiology Authors: Tremblay JC, Coombs GB, Howe CA, Vizcardo-Galindo G, Figueroa-Mujica RJ, Bermudez D, Tymko MM, Villafuerte FC, Ainslie PN, Pyke KE Tags: Am J Physiol Heart Circ Physiol Source Type: research

Aortic distensibility is associated with both resting and hyperemic coronary blood flow.
This study compared invasive measures of coronary blood flow (CBF) with cardiac magnetic resonance (CMR) derived aortic distensibility (AD). METHODS: Following coronary angiography, a Doppler FloWire and infusion microcatheter were advanced into the study vessel. Average peak velocity (APV) was acquired at baseline and following intracoronary adenosine to derive coronary flow velocity reserve (CFVR = hyperemic APV/resting APV), and CBF (π x [Diameter]2 x APV x 0.125). Following angiography, patients underwent CMR to evaluate distensibility at the ascending aorta (AA), proximal descending aorta (PDA) and distal desc...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 22, 2019 Category: Physiology Authors: Nelson AJ, Puri R, Nicholls SJ, Dundon BK, Richardson JD, Sidharta SL, Teo KS, Worthley SG, Worthley M Tags: Am J Physiol Heart Circ Physiol Source Type: research

Modelling arterial pulse waves in healthy ageing: a database for in silico evaluation of haemodynamics and pulse wave indices.
In conclusion, the publicly available PW database (DOI: 10.5281/zenodo.2633175) is a valuable resource for understanding CV determinants of PWs, and for the development and pre-clinical assessment of PW analysis algorithms. It is particularly useful because the exact CV properties which generated each PW are known. PMID: 31442381 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 22, 2019 Category: Physiology Authors: Charlton P, Mariscal Harana J, Vennin S, Li Y, Chowienczyk P, Alastruey J Tags: Am J Physiol Heart Circ Physiol Source Type: research

Exosomes derived from Induced Vascular Progenitor Cells Promote Angiogenesis in vitro and in an in vivo Rat Hindlimb Ischemia Model.
Abstract Induced vascular progenitor cells (iVPCs) were created as an ideal cell type for regenerative medicine and have been reported to positively promote collateral blood flow and improve cardiac function in a rat model of myocardial ischemia. Exosomes have emerged as a novel biomedicine that mimics the function of the donor cells. We investigated the angiogenic activity of exosomes from induced vascular progenitor cells (iVPC-Exo) as a cell-free therapeutic approach for ischemia. Exosomes from iVPCs and rat aortic endothelial cells (RAECs) were isolated using a combination of ultrafiltration and size-exclusion...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 15, 2019 Category: Physiology Authors: Johnson TK, Zhao L, Zhu D, Wang Y, Xiao Y, Oguljahan B, Zhao X, Kirlin WG, Yin L, Chilian WM, Liu D Tags: Am J Physiol Heart Circ Physiol Source Type: research

Guidelines for evaluating myocardial cell death.
sui T Abstract Cell death is a fundamental process in cardiac pathologies. Recent studies revealed multiple forms of cell death, and several of them have been demonstrated to underlie adverse cardiac remodeling and heart failure. With the expansion in the area of myocardial cell death and increasing concerns over rigor and reproducibility, it is important and timely to set a guideline for the best practices of evaluating myocardial cell death. There are six major forms of regulated cell death observed in cardiac pathologies namely apoptosis, necroptosis, mitochondrial-mediated necrosis, pyroptosis, ferroptosis, an...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 15, 2019 Category: Physiology Authors: Mishra PK, Adameová A, Hill JA, Baines CP, Kang PM, Downey J, Narula J, Takahashi M, Abbate A, Piristine HC, Kar S, Su S, Higa JK, Kawasaki NK, Matsui T Tags: Am J Physiol Heart Circ Physiol Source Type: research

-Cardiac intramural electrical mapping reveals focal delays but no conduction velocity slowing in the peri-infarct region.
This study characterises, for the first time, the intramural spread of electrical activation in the peri-infarct region of chronic reperfusion MIs. Four sheep were studied 13 weeks after antero-apical reperfusion infarction. Extracellular potentials (ECPs) were recorded in a ~20×20 mm2 region adjacent to the infarct boundary (25 plunge needles
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 15, 2019 Category: Physiology Authors: Trew ML, Engelman ZJ, Caldwell BJ, Lever NA, LeGrice IJ, Smaill BH Tags: Am J Physiol Heart Circ Physiol Source Type: research

Placental Growth Factor Levels in Quadriceps Muscle Are Reduced by a Western Diet in Association With Advanced Glycation End Products.
Abstract In peripheral artery disease (PAD), atherosclerotic occlusion chronically impairs limb blood flow. Arteriogenesis (collateral artery remodeling) is a vital adaptive response to PAD that protects tissue from ischemia. Type II diabetics have a high risk of developing PAD, and would benefit from arteriogenesis. However, arteriogenesis is suppressed in diabetics by a multifaceted mechanism which remains incompletely defined. Upregulation of placental growth factor (PLGF) is a key early step in arteriogenesis. Therefore, we hypothesized that metabolic dysfunction would impair PLGF expression in skeletal muscle...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 8, 2019 Category: Physiology Authors: Silva AT, Rouf F, Semola OA, Payton ME, Lovern PC Tags: Am J Physiol Heart Circ Physiol Source Type: research

Role of B1 and B2 Lymphocytes in Placental Ischemia-induced Hypertension.
Abstract Preeclampsia is a prevalent pregnancy complication characterized by new-onset maternal hypertension and inflammation, with placental ischemia as the initiating event. Studies of others have provided evidence for the importance of lymphocytes in placental ischemia-induced hypertension, however contributions of B1 vs. B2 lymphocytes are unknown. We hypothesized that peritoneal B1 lymphocytes are important for placental ischemia-induced hypertension. As an initial test of this hypothesis, the effect of anti-CD20 depletion on both B cell populations was determined in Reduced Utero-placental Perfusion Pressure...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 8, 2019 Category: Physiology Authors: Laule CF, Odean EJ, Wing CR, Root KM, Towner KJ, Hamm CM, Gilbert JS, Fleming SD, Regal JF Tags: Am J Physiol Heart Circ Physiol Source Type: research

Racial Disparities in Cardiovascular Disease Risk: Mechanisms of Vascular Dysfunction.
Abstract Cardiovascular disease (CVD) accounts for a third of all deaths in the United States making it the leading cause of morbidity and mortality. While CVD affects individuals of all races / ethnicities, the prevalence of CVD is highest in non-hispanic black individuals (BL) relative to other populations. The mechanism(s) responsible for elevated CVD risk in the BL population remains incompletely understood. However, impaired vascular vasodilator capacity and exaggerated vascular vasoconstrictor responsiveness are likely contributing factors, both of which are present even in young otherwise healthy BL. Within...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 8, 2019 Category: Physiology Authors: Brothers RM, Fadel PJ, Keller DM Tags: Am J Physiol Heart Circ Physiol Source Type: research

Detrimental Effects of Chemotherapy on Human Coronary Microvascular Function.
CONCLUSIONS: In vessels from adult subjects, acute treatment with Dox in clinically relevant doses caused significant impairment of coronary arteriolar function, whereas vessels from pediatric subjects showed only marginal impairment to the same stressor. This interesting finding might explain the delayed onset of future adverse CV events in children compared to adults after anthracycline therapy. PMID: 31397169 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Heart and Circulatory Physiology)
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 8, 2019 Category: Physiology Authors: Hader SN, Zinkevich NS, Norwood Toro LE, Kriegel AJ, Kong A, Freed JK, Gutterman DD, Beyer AM Tags: Am J Physiol Heart Circ Physiol Source Type: research

High-mannose intercellular adhesion molecule-1 (ICAM-1) enhances CD16+ monocyte adhesion to the endothelium.
Abstract Human monocytes have been classified into three distinct groups - classical (anti-inflammatory; CD14+/CD16-), non-classical (patrolling; CD14+/CD16++), and intermediate (pro-inflammatory; CD14++/CD16+). Adhesion of non-classical / intermediate monocytes with the endothelium is important for innate immunity, and also vascular inflammatory disease. However, there is an incomplete understanding of the mechanisms that regulate CD16+ vs. CD16- monocyte adhesion to the inflamed endothelium. Here, we tested the hypothesis that a high mannose (HM) N-glycoform of intercellular adhesion molecule-1 (ICAM-1) on the e...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 8, 2019 Category: Physiology Authors: Regal-McDonald K, Xu B, Barnes JW, Patel RP Tags: Am J Physiol Heart Circ Physiol Source Type: research

Hyperphosphatemia is Required for Initiation, but not Propagation, of Kidney Failure-Induced Calcific Aortic Valve Disease.
Abstract High serum levels of phosphate are associated with uraemia-induced calcific aortic valve disease (CAVD). However, it is not clear whether hyperphosphataemia is required in all phases of the process. Our aim was to determine the effects of phosphate and phosphate depletion at different phases of valve disease. The experimental design consisted of administering a uraemia-inducing diet, with or without phosphate enrichment, to rats for 7 weeks. Forty-two rats were fed with a phosphate-enriched uraemic regimen that caused renal insufficiency and hyperphosphataemia. Another 42 rats were fed with a phosphate-de...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 8, 2019 Category: Physiology Authors: Shuvy M, Abedat S, Eliaz R, Abu-Rmeileh I, Abu-Snieneh A, Ben Dov IZ, Meir K, Pereg D, Beeri R, Lotan C Tags: Am J Physiol Heart Circ Physiol Source Type: research

ATP-dependent chromatin remodeling complexes in embryonic vascular development and hypertension.
Abstract Hypertension, a chronic elevation in blood pressure, is the largest single contributing factor to mortality worldwide and the most common preventable risk factor for cardiovascular disease. High blood pressure increases the risk for someone to experience a number of adverse cardiovascular events including heart failure, stroke, or aneurysm. Despite advancements in understanding factors that contribute to hypertension, the etiology remains elusive and there remains a critical need to develop innovative study approaches in order to develop more effective therapeutics. ATP-dependent chromatin remodelers are ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 8, 2019 Category: Physiology Authors: Crosswhite PL Tags: Am J Physiol Heart Circ Physiol Source Type: research

Right Ventricular Oxygen Delivery as a Determinant of Right Ventricular Functional Reserve during Exercise in Juvenile Swine with Chronic Pulmonary Hypertension.
In this study, we aim to establish RV-oxygen (O2) deliveryas a determinant for RV-functional reserve during exercise in swine with chronic PH. METHODS AND RESULTS: Chronic PH was induced by pulmonary vein banding (PVB), with sham operation serving as control. RV function and RV-O2delivery were measured over time in chronically instrumented swine, up to 12 weeks after PVB at rest and during exercise. At rest, RV afterload (pulmonary artery pressure and Ea) and contractility (Ees and dP/dtmax) were higher in PH compared with control with preserved cardiac index and RV-O2delivery. However, RV-functional reserve, as measu...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 8, 2019 Category: Physiology Authors: Cai Z, van Duin RWB, Stam K, Uitterdijk A, van der Velden J, Vonk-Noordegraaf A, Duncker DJ, Merkus D Tags: Am J Physiol Heart Circ Physiol Source Type: research

Optimized Protocols for Isolation, Fixation and Flow Cytometric Characterization of Leukocytes in Ischemic Hearts.
Abstract Immune activation post-myocardial infarction is an orchestrated sequence of cellular responses to effect tissue repair and healing. However, excessive and dysregulated inflammation can result in left ventricular remodeling and pathological alterations in the structural and mechanical attributes of the heart. Identification of key pathways and critical cellular mediators of inflammation is thus essential to design immunomodulatory therapies for myocardial infarction and ischemic heart failure. Despite this, the experimental approaches to isolate mononuclear cells from the heart are diverse, and detailed pr...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 1, 2019 Category: Physiology Authors: Covarrubias R, Ismahil MA, Rokosh G, Hamid T, Accornero F, Singh H, Gumina RJ, Prabhu S, Bansal S Tags: Am J Physiol Heart Circ Physiol Source Type: research

Asynchronous action potential discharge in human muscle sympathetic nerve activity.
Abstract What strategies are employed by the sympathetic system to communicate with the circulation? Muscle sympathetic nerve activity (MSNA) occurs in bursts of synchronous action potential (AP) discharge, yet whether between-burst asynchronous AP firing exists remains unknown. Using multi-unit microneurography and a continuous wavelet transform to isolate APs, we studied AP synchronicity within human MSNA. Asynchronous APs were defined as those which occurred between bursts. Experiment One quantified AP synchronicity in eight individuals at baseline (BSL), -10 mmHg lower body negative pressure (LBNP), -40 mmHg L...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 1, 2019 Category: Physiology Authors: Klassen SA, Moir ME, Limberg JK, Baker SE, Nicholson WT, Curry TB, Joyner MJ, Shoemaker JK Tags: Am J Physiol Heart Circ Physiol Source Type: research

Cardiac Troponin I Phosphorylation Underlies Myocardial Contractile Dysfunction Induced by Hypothermia-Rewarming.
Abstract Rewarming the intact heart after a period of hypothermia is associated with reduced myocardial contractility, decreased Ca2+ sensitivity and increased cardiac troponin I (cTnI) phosphorylation. We hypothesized that hypothermia/rewarming (H/R) induces left ventricular (LV) contractile dysfunction due to phosphorylation of cTnI at Ser 23/24. To test this hypothesis, the response of wildtype mice (n=7) to H/R was compared to transgenic mice expressing slow skeletal TnI (TG-ssTnI; n=7) that lacks the Ser 23/24 phosphorylation sites. Hypothermia was induced by surface cooling and maintained at 23-25ºC for...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 1, 2019 Category: Physiology Authors: Tveita T, Arteaga GM, Han YS, Sieck GC Tags: Am J Physiol Heart Circ Physiol Source Type: research

Dilated cardiomyopathy mutation (R174W) in troponin T attenuates the length-mediated increase in crossbridge recruitment and myofilament Ca2+ sensitivity.
In this study, we investigated the effect of DCM-linked mutation (R173W) in human cardiac troponin T (TnT) on myofilament LDA. R173W mutation is associated with left ventricular dilatation and systolic dysfunction, and is found in multiple families. R173W mutation is in the central region (residues 80-180) of TnT, which is known to be important for myofilament cooperativity and crossbridge (XB) recruitment. Steady-state and dynamic contractile parameters were measured in detergent-skinned guinea pig left ventricular muscle fibers reconstituted with recombinant guinea pig wild-type TnT (TnTWT) or mutant TnT (TnTR174W; guine...
Source: American Journal of Physiology. Heart and Circulatory Physiology - August 1, 2019 Category: Physiology Authors: Reda SM, Chandra M Tags: Am J Physiol Heart Circ Physiol Source Type: research

Cardiac remodeling after six weeks of high-intensity interval training to exhaustion in endurance-trained males.
Brassard P Abstract High-intensity interval training (HIIT) improves physical performance of endurance athletes, although studies examining its cardiovascular effects are sparse. We evaluated the impact of HIIT on blood pressure, heart rate and cardiac cavities size and function in endurance-trained adults. Seventeen endurance-trained males underwent 24-hour ambulatory blood pressure monitoring (ABPM) and Doppler echocardiography at baseline and after 6 weeks of HIIT. Participants were divided in 2 groups (85% maximal aerobic power (MP); HIIT85, n=8 and 115% MP; HIIT115 , n = 9) in order to compare the impact of ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 25, 2019 Category: Physiology Authors: Mahjoub H, Le Blanc O, Paquette M, Imhoff S, Labrecque L, Drapeau A, Poirier P, Bédard É, Pibarot P, Brassard P Tags: Am J Physiol Heart Circ Physiol Source Type: research

Impact of heart rate on cross-bridge cycling kinetics in failing and non-failing human myocardium.
Abstract The force-frequency relationship (FFR) is an important regulatory mechanism that increases the force-generating capacity as well as the contraction and relaxation kinetics in human cardiac muscle as the heart rate increases. In human heart failure, the normally positive FFR often becomes flat, or even negative. The rate of cross-bridge cycling, which has been reported to affect cardiac output, could be potentially dysregulated and contribute to blunted or negative FFR in heart failure. We recently developed and here use a novel method for measuring the rate of tension redevelopment (ktr). This method allo...
Source: American Journal of Physiology. Heart and Circulatory Physiology - July 25, 2019 Category: Physiology Authors: Chung JH, Milani-Nejad N, Davis JP, Weisleder N, Whitson BA, Mohler PJ, Janssen PML Tags: Am J Physiol Heart Circ Physiol Source Type: research