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PubMed Journal Database | American journal of physiology. Heart and circulatory physiology - Page: 4 RSS

11:36 EST 9th December 2019 | BioPortfolio

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Showing PubMed Articles 76–100 of 513 from American journal of physiology. Heart and circulatory physiology

Hydrogen sulfide-mediated regulation of cell death signaling ameliorates adverse cardiac remodeling and diabetic cardiomyopathy.

The death of cardiomyocytes is a precursor for the cascade of hypertrophic and fibrotic remodeling that leads to cardiomyopathy. In diabetes mellitus (DM), the metabolic environment of hyperglycemia, hyperlipidemia, and oxidative stress causes cardiomyocyte cell death leading to diabetic cardiomyopathy (DMCM), an independent cause of heart failure. Understanding the roles of the cell death signaling pathways involved in the development of cardiomyopathies is crucial to the discovery of novel targeted therap...

Strength-Duration Relationship as a Tool to Prioritize Cardiac Tissue Properties that Govern Electrical Excitability.

Engineered cardiac tissue and cardiomyocyte cell cultures offer wide opportunities for improved therapeutic intervention and laboratory heart models. Electric field excitation is a common intervention in the production of engineered tissue and the investigation of the electrical properties of in vitro cell cultures. In this work, we use strength-duration relationships to systematically investigate factors influencing electrical excitability of 2D and 3D neonatal rat ventricular myocyte cultures. We find tha...

Activated T effector seeds: Cultivating atherosclerotic plaque through alternative activation.

Atherosclerosis is a chronic inflammatory pathology that precipitates substantial morbidity and mortality. Though initiated by physiologic patterns of low and disturbed flow that differentially prime endothelial cells at sites of vessel branch points and curvature, the chronic, smoldering inflammation of atherosclerosis is accelerated by comorbidities involving inappropriate activation of the adaptive immune system, such as autoimmunity. The innate contributions to atherosclerosis, especially in the transit...

Apoptosis signal-regulating kinase 1 activation by Nox1-derived oxidants is required for TNFα receptor endocytosis.

Tumor necrosis factor-α (TNFα) is pro-inflammatory cytokine that is closely linked to the development of cardiovascular disease. TNFα activates NADPH oxidase 1 (Nox1), and reactive oxygen species (ROS) including superoxide (O) production extracellularly are required for subsequent signaling in vascular smooth muscle cells (VSMC). Apoptosis signal-regulating kinase 1 (ASK1) is a MAPKKK that is activated by oxidation of associated thioredoxin. The role of ASK1 in Nox1-mediated signaling by TNFα is poorly ...

The (Pro)renin Receptor Knockdown in the Paraventricular Nucleus of Hypothalamus Attenuates Hypertension Development and AT Receptor-Mediated Calcium Events.

Activation of the brain renin-angiotensin system (RAS) is a pivotal step in the pathogenesis of hypertension. The paraventricular nucleus (PVN) of the hypothalamus is a critical part of the angiotensinergic sympatho-excitatory neuronal network involved in neural control of blood pressure and hypertension. However, the importance of the PVN (pro)renin receptor (PVN-PRR)-a key component of the brain RAS-in hypertension development has not been examined. In this study, we investigated the involvement and mecha...

Ablation of Cardiac TIGAR Preserves Myocardial Energetics and Cardiac Function in the Pressure Overload Heart Failure Model.

Despite the advances in medical therapy, the morbidity and mortality of heart failure (HF) remain unacceptably high. HF results from reduced metabolism-contraction coupling efficiency, so the modulation of cardiac metabolism may be an effective strategy for therapeutic interventions. Tumor suppressor p53 and its downstream target TP53-induced glycolysis and apoptosis regulator (TIGAR) are known to modulate cardiac metabolism and cell fate. In order to investigate TIGAR's function in HF, we compared myocardi...

Novel approach for quantification of endoplasmic reticulum Ca transport.

The type 2a sarco/endoplasmic reticulum Ca-ATPase (SERCA2a) plays a key role in Ca regulation in the heart. However, available techniques to study SERCA function are either cell destructive or lack sensitivity. The goal of this study was to develop an approach to selectively measure SERCA2a function in the cellular environment. The genetically encoded Ca sensor R-CEPIA1er was used to measure the concentration of Ca in the lumen of the endoplasmic reticulum (ER) ([Ca]) in HEK293 cells expressing human SERCA2...

Role of T-cell Activation in Salt-sensitive Hypertension.

The contributions of T lymphocytes to the pathogenesis of salt-sensitive hypertension has been well established. Under hypertensive stimuli, naïve T cells develop into different subsets, including Th1, Th2, Th17, Treg and cytotoxic CD8 T cells, depending on the surrounding microenviroment in organs. Distinct subsets of T cells may play totally different roles in tissue damage and hypertension. The underlying mechanisms by which hypertensive stimuli activate naïve T cells involve many events and different ...

Vascular phenotype of amyloid precursor protein-deficient mice.

The amyloid precursor protein (APP) is expressed in blood vessel wall but the physiological function of APP is not completely understood. Moreover, previous studies established that APP has amine oxidase activity responsible for degradation of catecholamines. In the present study, we characterized vascular phenotype of APP-knockout (APP) mice. We demonstrate that circulating levels of catecholamines are significantly increased in male as compared to female APP mice. Studies of vasomotor function in isolated...

MK5 haplodeficiency decreases collagen deposition and scar size during post-myocardial infarction wound repair.

MK5 is a protein serine/threonine kinase activated by p38, ERK3, and ERK4 MAPKs. MK5 mRNA and immunoreactivity are detected in mouse cardiac fibroblasts and MK5-haplodeficiency attenuates the increase in collagen 1-a1 mRNA evoked by pressure overload. The present study examined the effect of MK5 haplodeficiency on reparative fibrosis following myocardial infarction (MI). Twelve-week-old MK5 and wild-type littermate (MK5) mice underwent ligation of the left anterior descending coronary artery (LADL). Survivi...

Maternal High-Fat, High-Sucrose Diet Induces Transgenerational Cardiac Mitochondrial Dysfunction Independent of Maternal Mitochondrial Inheritance.

Maternal obesity is correlated with cardiovascular disease in offspring, with 1.3-fold increase in events observed in offspring of obese women. We have observed that obesity-exposed oocytes demonstrate impaired mitophagy and transmit damaged mitochondria to the offspring. Accordingly, we hypothesized that maternal obesity induces cardiac mitochondrial dysfunction in the offspring via transgenerational inheritance of abnormal oocyte mitochondria. We mated female mice fed a high-fat/high-sucrose (HFS) diet (o...

Hemodynamic characterization of a transgenic rat strain stably expressing the calcium sensor protein GCaMP2.

A novel transgenic rat strain has recently been generated that stably expresses the genetically engineered calcium sensor protein GCaMP2 in different cell types including cardiomyocytes to investigate calcium homeostasis. In order to investigate whether the expression of the GCaMP2 protein itself affects cardiac function, in the present work we aimed at characterizing in vivo hemodynamics in the GCaMP2 transgenic rat strain. GCaMP2 transgenic rats and age-matched Sprague-Dawley control animals were investig...

Role of endothelial NAD+ deficiency in age-related vascular dysfunction.

Age-related alterations in endothelium and the resulting vascular dysfunction critically contribute to a range of pathological conditions associated with old age. To rationally develop therapies that improve vascular health and thereby increase health span and lifespan in older adults, it will be essential to understand the cellular and molecular mechanisms contributing to vascular aging. Pre-clinical studies in model organisms demonstrate that NAD availability decreases with age in multiple tissues and tha...

Development of a decerebrate model for investigating mechanisms mediating viscero-sympathetic reflexes in the spinalized rat.

Autonomic dysreflexia (AD) often occurs in individuals living with spinal cord injury (SCI) and is characterized by uncontrolled hypertension in response to otherwise innocuous stimuli originating below the level of the spinal lesion. Visceral stimulation is a predominate cause of AD in humans, and effectively replicates the phenotype in rodent models of SCI. Direct assessment of sympathetic responses to viscerosensory stimulation in spinalized animals is challenging and requires invasive surgical procedure...

Right Ventricular and Pulmonary Vascular Changes in Pulmonary Hypertension Associated with Left Heart Disease.

Zebrafish model of amyloid light chain cardiotoxicity: regeneration vs degeneration.

Cardiac dysfunction is the most frequent cause of morbidity and mortality in immunoglobulin light chain (AL) amyloidosis. Previously published transgenic animal models of AL amyloidosis have not recapitulated the key phenotype of cardiac dysfunction seen in AL amyloidosis which has limited our understanding of the disease mechanisms in vivo, as well as the development of targeted AL therapeutics. We have developed a transgenic zebrafish model in which a AL patient-derived lambda light chain (LC) is conditio...

Conduction in the Right and Left Ventricle is Differentially Regulated by Protein Kinases and Phosphatases: Implications for Arrhythmogenesis.

The "stress kinases" cAMP-dependent protein kinase (PKA) and calcium/calmodulin-dependent protein kinase II (CaMKII), phosphorylate the Nachannel Nav1.5 subunit to regulate its function. However, how the channel regulation translates to ventricular conduction is poorly understood. We hypothesized that the stress kinases positively and differentially regulate conduction in the right (RV) and the left (LV) ventricles. We applied CaMKII blocker KN93 (2.75 mM), PKA blocker H89 (10 mM), and broad-acting phosphat...

Shaping the future heart: transgenerational outcomes of maternal metabolic syndrome.

Understanding Sex Differences in Long-term Blood Pressure Regulation: Insights from Experimental Studies and Computational Modeling.

Sex differences in blood pressure and the prevalence of hypertension are found in humans and animal models. Moreover, there has been a recent an explosion of data concerning sex differences in nitric oxide, the renin-angiotensin-aldosterone system, inflammation, and kidney function. These data have the potential to reveal the mechanisms underlying male-female differences in blood pressure control. To elucidate the interactions among the multitude of physiological processes involved, one may apply computatio...

Inorganic Arsenic Exposure Induces Sex Disparate Effects and Exacerbates Ischemia-Reperfusion Injury in the Female Heart.

Arsenic is a common contaminant in drinking water throughout the world, and recent studies support a link between inorganic arsenic (iAS) exposure and ischemic heart disease in men and women. Female hearts exhibit an estrogen-dependent reduction in susceptibility to myocardial ischemic injury compared to males, and as such, female hearts may be more susceptible to the endocrine disrupting effects of iAS exposure. However, iAS exposure and susceptibility to ischemic heart injury have not been examined in mec...

Differences in pulmonary arterial flow hemodynamics between children and adults with pulmonary arterial hypertension as assessed by 4D-flow CMR studies.

Despite different developmental and pathologic processes affecting lung vascular remodeling in both patient populations, differences in 4D-MRI findings between children and adults with PAH have not been studied. The purpose of this study was to compare flow hemodynamic state, including flow-mediated shear forces, between pediatric and adult patients with PAH matched by severity of pulmonary vascular resistance index (PVRi). Adults (n=10) and children (n=10) with PAH matched by pulmonary vascular resistance ...

Beneficial Effects of Mesenchymal Stem Cell Delivery via a Novel Cardiac Bioscaffold on Right Ventricles of Pulmonary Arterial Hypertensive Rats.

Right ventricular failure (RVF) is a common cause of death in patients suffering from pulmonary arterial hypertension (PAH). The current treatment for PAH only moderately improves symptoms and RVF ultimately occurs. Therefore, it is necessary to develop new treatment strategies to protect against RV maladaptation despite PAH progression. In this study, we hypothesize that local mesenchymal stem cell (MSC) delivery via a novel bioscaffold can improve RV function despite persistent PAH. To test our hypothesis...

Muscle Metaboreflex - Induced Central Blood Volume Mobilization in Heart Failure.

Underperfusion of active skeletal muscle causes metabolites to accumulate and stimulate group III and IV skeletal muscle afferents which triggers a powerful pressor response termed the muscle metaboreflex. Muscle metaboreflex activation (MMA) during submaximal dynamic exercise in healthy individuals increases arterial pressure mainly via substantial increases in cardiac output (CO). The increases in CO occur via the combination of tachycardia and increased ventricular contractility. Importantly, MMA also el...

Angiotensin Type 2 Receptor Stimulation With Compound 21 Improves Neurological Function after Stroke In Female Rats: A Pilot Study.

The angiotensin II type 2 receptor (AT2R) agonist, compound 21 (C21), has been shown to be neurovascular protective after ischemic stroke in male rats. In the current study, we aim to study the impact of C21 treatment on female rats. Young female Wistar rats were subjected to different durations of middle cerebral artery occlusion (MCAO) (3 h, 2 h and 1 h) using a silicone-coated monofilament, treated at reperfusion with Intraperitoneal C21 0.03 mg/kg and followed up for different times (1, 3 and 14 days) a...

Reflected hemodynamic waves influence the pattern of Doppler ultrasound waveforms along the umbilical arteries.

The pulsatile pattern of blood motion measured by Doppler ultrasound within the umbilical artery is known to contain useful diagnostic information and is widely used to monitor pregnancies at risk of fetal growth restriction or stillbirth. Animal studies have identified reflected pressure waves travelling counter to the direction of blood flow as an important factor in the shape of these waveforms. In the present study, we establish a method to measure reflected waves in the human umbilical artery and asses...


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