A5088618033- Ion Channels and Receptors
- Pulmonary Hypertension Research and Treatments
- Nitric Oxide and Endothelin Effects
- Angiogenesis and VEGF in Cancer
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Sodium Intake and Health
- Heart Rate Variability and Autonomic Control
- Congenital heart defects research
- Mitochondrial Function and Pathology
- Cerebrovascular and genetic disorders
- Magnesium in Health and Disease
- Thermoregulation and physiological responses
- Pancreatic function and diabetes
- Lymphatic System and Diseases
- Zebrafish Biomedical Research Applications
- Metabolism, Diabetes, and Cancer
- Neonatal Respiratory Health Research
- ATP Synthase and ATPases Research
- Neuroscience of respiration and sleep
- Diabetes Treatment and Management
- Hemoglobin structure and function
- Protein Kinase Regulation and GTPase Signaling
University of Virginia
2016-2022
Dalian Medical University
2016
Washington University in St. Louis
2016
Universidade Federal do Espírito Santo
2016
University of Cincinnati
2015
Background: Impaired endothelium-dependent vasodilation is a hallmark of obesity-induced hypertension. The recognition that Ca 2+ signaling in endothelial cells promotes has led to the hypothesis compromised during obesity, but underlying abnormality unknown. In this regard, transient receptor potential vanilloid 4 (TRPV4) ion channels are major influx pathway cells, and regulatory protein AKAP150 (A-kinase anchoring 150) enhances activity TRPV4 channels. Methods: We used...
Recent studies have focused on the contribution of capillary endothelial TRPV4 channels to pulmonary pathologies, including lung edema and injury. However, in hypertension (PH), small arteries are focus pathology, this crucial anatomy remain unexplored PH. Here, we provide evidence that cell caveolae maintain a low arterial pressure under normal conditions. Moreover, activity caveolar is impaired from mouse models PH patients. In PH, up-regulation iNOS NOX1 enzymes at results formation...
Abstract During blood vessel development, endothelial cells become specified toward arterial or venous fates to generate a circulatory network that provides nutrients and oxygen to, removes metabolic waste from, all tissues. Arterial-venous specification occurs in conjunction with suppression of cell cycle progression; however, the mechanistic role state is unknown. Herein, using Cdh5-CreER T2 ;R26FUCCI2aR reporter mice, we find are enriched for FUCCI-Negative (early G1) BMP signaling, while...
Recent studies demonstrate that spatially restricted, local Ca2+ signals are key regulators of endothelium-dependent vasodilation in systemic circulation. There drastic functional differences between pulmonary arteries (PAs) and arteries, but the control PAs not known. Localized, unitary influx events through transient receptor potential vanilloid 4 (TRPV4) channels, termed TRPV4 sparklets, regulate resistance-sized mesenteric via activation Ca2+-dependent K+ channels. The objective this...
Objective— Several physiological stimuli activate smooth muscle cell (SMC) G q PCRs (G protein–coupled receptors) to cause vasoconstriction. As a protective mechanism against excessive vasoconstriction, SMC PCR stimulation invokes endothelial vasodilatory signaling. Whether Ca 2+ influx in cells contributes the regulation of PCR-induced vasoconstriction remains unknown. through TRPV4 (transient receptor potential vanilloid 4) channels is key regulator endothelium-dependent vasodilation. We...
The ability of hemoglobin to scavenge the potent vasodilator nitric oxide (NO) in blood has been well established as a mechanism vascular tone homeostasis. In endothelial cells, alpha chain (hereafter, globin) and NO synthase form macromolecular complex, providing sink for directly adjacent production source. We have developed an globin mimetic peptide (named HbαX) that displaces endogenous increases bioavailable vasodilation. Here we show that, vivo, HbαX administration capillary...
Both glucagon-like peptide-1 (GLP-1) and apolipoprotein A-IV (apoA-IV) are produced from the gut enhance postprandial insulin secretion. This study investigated whether apoA-IV regulates nutrient-induced GLP-1 secretion knockout causes compensatory release. Using lymph-fistula-mice, we first determined lymphatic by administering before an intraduodenal Ensure infusion. changed neither basal nor Ensure-induced relative to saline administration. We then assessed in apoA-IV−/− wild-type (WT)...
Summary Formation and maturation of a functional blood vascular system is required for the development maintenance all tissues in body. During process vessel development, primordial endothelial cells are formed become specified toward arterial or venous fates to generate circulatory network that provides nutrients oxygen to, removes metabolic waste from, 1-3 . Specification occurs conjunction with suppression cell cycle progression 4,5 , hyperproliferation associated potentially lethal...
We previously demonstrated that the transcription factor Grainyhead-like 3 (GRHL3) has essential functions in endothelial cells by inhibiting apoptosis and promoting migration as well activation of nitric oxide synthase (eNOS). now show a large portion protein is localized to myo-endothelial projections murine arteries suggesting extra-nuclear functions. Therefore, we generated various deletion mutants identify nuclear localization signal (NLS) GRHL3 assessed potential Several large-scale...
Localized, spatially restricted Ca 2+ signals promote endothelium‐dependent vasodilation in systemic and pulmonary microcirculation. Unitary influx through endothelial transient receptor potential vanilloid 4 (TRPV4) channels, termed TRPV4 sparklets, resistance arteries. sparklets dilate small mesenteric arteries (MAs) via activation of intermediate conductance ‐activated K + (IK SK, respectively) (PAs) nitric oxide synthase (eNOS) activation. Although is known to activate different...
Impaired endothelium‐dependent vasodilation is a key contributor to elevated pulmonary arterial pressure (PAP) in hypertension (PH). While the mechanisms of pathogenesis PH remain elusive, recent studies show that spatially localized Ca 2+ influx via endothelial transient receptor potential vanilloid 4 (TRPV4 EC ) channels promotes resistance‐sized arteries (PAs) by activating nitric oxide synthase (eNOS) and releasing (NO). Caveolin‐1 (Cav‐1 an essential structural protein within...
The endothelium is an important regulator of vascular resistance and overall pulmonary arterial pressure (PAP). Endothelial dysfunction in small, arteries (PAs) leads to impaired vasodilation, increased PAP, the development hypertension (PH). However, mechanisms leading endothelial PH remain unknown. We recently identified TRPV4 (transient receptor potential vanilloid 4‐TRPV4 EC ) channels as regulators endothelium‐dependent vasodilation small PAs, showed that localized Ca 2+ influx events...
Endothelial dysfunction is a hallmark of pulmonary disorders including hypertension, edema, acute lung injury and ischemia. Ca 2+ influx through TRPV4 (transient receptor potential vanilloid 4) channels plays an important role in regulating the function endothelium, abnormal channel activity has been associated with injury, ischemia, edema. However, their regulation by physiological stimuli endothelium remain unknown. The objectives this study were to elucidate under conditions; identify...
Endothelial cells (ECs) play a crucial role in regulating vascular function. Weakening of local Ca 2+ signaling networks the ECs leads to loss endothelial vasodilation hypertension (Sonkusare et al., Science Signaling, 2014). There is increasing evidence that obesity also associated with The objective this study was determine impact diet‐induced (DIO) on regulate vasodilation. We recently showed elementary influx events through TRPV4 (transient receptor potential vanilloid 4) channels (TRPV4...
Vasodilatory function of endothelial cells (ECs) is regulated by localized increases in intracellular Ca 2+ . TRPV4 (transient receptor potential vanilloid 4) channels on the EC membrane are a major influx pathway systemic and pulmonary endothelium, key determinant vasodilations to physiological stimuli. We recently showed that localized, unitary events through (TRPV4 sparklets) membranes dilate resistance‐sized arteries (PAs) selective activation nitric oxide synthase (eNOS) (Marziano et...
Endothelial cell (EC) Ca 2+ is a key regulator of endothelial vasodilations. ECs negatively regulate the vasoconstrictions caused by sympathetic nerve stimulation or activation α 1 ‐adrenergic receptors (α ARs) on smooth muscle cells (SMCs). Previous studies have indicated that G q‐ protein coupled ARs generates inositol trisphosphate (IP 3 ) and in SMCs, which can be transported to through myoendothelial gap junctions. This results an increase EC thereby generating dilatory signal opposes...
Endothelial dysfunction contributes to the pathogenesis of pulmonary arterial hypertension (PAH) by reducing vasodilation. Endothelium‐dependent vasodilation is an important regulator vascular resistance (PVR) and overall pressure (PAP). We recently identified endothelial TRPV4 (transient receptor potential vanilloid 4) channels as regulators in arteries (PAs), showed that unitary Ca 2+ influx events through channels, termed sparklets, activate nitric oxide synthase (eNOS) cause Reduced NO...
Obesity‐induced endothelial dysfunction contributes to the development of cardiovascular abnormalities. Although Ca 2+ signaling is well‐known regulate endothelium‐dependent vasodilation in small arteries, whether mechanisms are impaired obesity remains unknown. We recently showed that unitary influx through TRPV4 (transient receptor potential vanilloid 4) channels, termed sparklets, elicits activation ‐sensitive K + (IK and SK) channels. A kinase anchoring protein 150 (AKAP150), which can...
Background: Pulmonary hypertension (PH) is a degenerative disorder that characterized by elevated vascular resistance and pulmonary arterial pressure (PAP). Endothelial transient receptor potential vanilloid 4 (TRPV4 EC ) ion channels represent an important Ca 2+ influx signaling mechanism promotes vasodilation of small arteries (PAs). Scaffolding protein caveolin-1 (Cav-1) has been shown to precipitate with TRPV4 in endothelial cells culture. Hypothesis: We hypothesized the Cav-1-TRPV4...