A5036315752- Nitric Oxide and Endothelin Effects
- Connexins and lens biology
- Caveolin-1 and cellular processes
- Erythrocyte Function and Pathophysiology
- Cardiovascular Health and Disease Prevention
- High Altitude and Hypoxia
- Atherosclerosis and Cardiovascular Diseases
- Ion Transport and Channel Regulation
- Renin-Angiotensin System Studies
- Ion Channels and Receptors
- Thermoregulation and physiological responses
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Hemoglobin structure and function
- Redox biology and oxidative stress
- Peroxisome Proliferator-Activated Receptors
- Lipid Membrane Structure and Behavior
- Heme Oxygenase-1 and Carbon Monoxide
- Cardiovascular Disease and Adiposity
- Adipose Tissue and Metabolism
- Angiogenesis and VEGF in Cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Biomarkers in Disease Mechanisms
- Cell Adhesion Molecules Research
University of Virginia
2019-2024
Increasing prevalence of obesity and its associated risk with cardiovascular diseases demands a better understanding the contribution different cell types within this complex disease for developing new treatment options. Previous studies could prove fundamental role FTO (fat mass obesity-associated protein) obesity; however, functional is less understood.We identify endothelial as previously unknown central regulator both obesity-induced metabolic vascular alterations.We generated...
A pathway underlying the TNFα-induced decrease in endothelial barrier function is found veins but not arteries.
Abstract Resistance artery vasodilation in response to hypoxia is essential for matching tissue oxygen and demand. In hypoxia, erythrocytic hemoglobin tetramers produce nitric oxide through nitrite reduction. We hypothesized that the alpha subunit of expressed endothelium also facilitates reduction proximal smooth muscle. Here, we create two mouse strains test this: an endothelial-specific globin knockout (EC Hba1Δ/Δ) another with allele mutated prevent globin’s inhibitory interaction...
Resistance arteries and conduit rely on different relative contributions of endothelial-derived hyperpolarization versus nitric oxide to achieve dilatory heterocellular signaling. Anatomically, resistance use myoendothelial junctions (MEJs), endothelial cell projections that make contact with smooth muscle cells. Conduit have very few no MEJs.Determine if the presence MEJs in can alter signaling.We previously demonstrated PAI-1 (plasminogen activator inhibitor-1) regulate formation MEJs....
Abstract During obesity, endothelial cells (ECs) become lipid laden leading to dysfunction. We demonstrate endothelium downregulates caveolin-1 (Cav1) in mouse and human response obesity. Using an EC-specific Cav1 knockout mouse, we find mice are hyperlipidemic regardless of diet, but retain cell function. Whereas initially this was thought be due mediate endocytosis, instead the have significantly increased nitric oxide (NO) lack Cav1. The presence or absence NO toggled inversely EC content...
Abstract Obesity is a multifactorial metabolic disorder associated with endothelial dysfunction and increased risk of cardiovascular disease. Adipose capillary adipose cells (CaECs) plays crucial role in lipid transport storage. Here, we investigated the mechanisms underlying CaEC-adipocyte interaction its impact on function. Single-cell RNA sequencing (scRNAseq) revealed an enrichment fatty acid handling machinery CaECs from high fat diet (HFD) mice, suggesting their specialized metabolism....
Lipid regulation of ion channels is largely explored using in silico modeling with minimal experimentation intact tissue; thus, the functional consequences these predicted lipid-channel interactions within native cellular environments remain elusive. The goal this study to investigate how lipid endothelial Kir2.1 - an inwardly rectifying potassium channel that regulates membrane hyperpolarization contributes vasodilation resistance arteries. First, we show phosphatidylserine (PS) localizes a...
Abstract Small artery vasodilation in response to hypoxia is essential for matching oxygen supply tissue demand. One source of hypoxic dilation via nitric oxide (NO) signaling nitrite reduction by erythrocytic hemoglobin (α2β2). However, the alpha subunit also expressed resistance endothelium and localized myoendothelial junctions, a subcellular domain that contacts underlying vascular smooth muscle cells. We hypothesized mediated endothelial globin may occur at junctions regulate...
Resistance arteries use different dilatory heterocellular signaling mechanisms than conduit (endothelial derived hyperpolarization versus nitric oxide). Anatomically, resistance myoendothelial junctions (MEJs), endothelial cell (EC) extensions that make contact with smooth muscle cells (SMCs), which are not present in arteries. The objective of this study was to determine if the presence MEJs can alter signaling. We previously demonstrated plasminogen activator inhibitor‐1 (PAI‐1) regulate...
The regulation of vasoconstriction and vasodilatory pathways is essential in resistance arteries, can be modulated by heterocellular communication between the endothelial smooth muscle cells. This occur via direct endothelial‐smooth cell contact at myoendothelial junctions (MEJs) through fenestrations internal elastic lamina (IEL). While it has been demonstrated that MEJs do not occupy every fenestration, their spatial distribution throughout endothelium yet defined could reveal localization...
In resistance arteries, matrix-devoid holes in the internal elastic lamina (HIEL) are presumably always site of endothelial and smooth muscle contact (myoendothelial junction; MEJs). MEJs signaling microdomains we have previously demonstrated that specific protein localization regulates heterocellular communication. However, it is time consuming to localize proteins at MEJ as requires electron microscopy (EM) verification-it also lacks quantitative analysis for spatial both within cells...
In large conduit arteries, smooth muscle cell elastin produces elastic laminae, while in resistance arteries endothelial derived is the major contributor to internal lamina (IEL). The IEL separates and endothelium contain distinct holes (HIEL) where two types communicate via a structure termed myoendothelial junction (MEJ). MEJ an anatomical hallmark of that pierces through facilitates vasodilation by movement hyperpolarization (EDH) muscle. contrast, dilate nitric oxide (NO) do not MEJs. To...
Abstract In the resistance artery endothelium, we show phosphatidylserine (PS) localizes to a specific subpopulation of myoendothelial junctions (MEJs), signaling microdomains that regulate vasodilation. silico data has implied PS may compete with PIP 2 binding on Kir2.1, channel involved in vasodilatory signaling. We found 83.33% Kir2.1-MEJs also contained PS, possibly indicating an interaction where regulates Kir2.1. Electrophysiology experiments HEK cells demonstrate blocks activation and...