A5102739437- Cardiovascular Function and Risk Factors
- Nitric Oxide and Endothelin Effects
- Cardiac Imaging and Diagnostics
- Cardiac Fibrosis and Remodeling
- Cardiovascular Disease and Adiposity
- Angiogenesis and VEGF in Cancer
- Alzheimer's disease research and treatments
- Lymphatic System and Diseases
- Neurological Disease Mechanisms and Treatments
- Protease and Inhibitor Mechanisms
- Dementia and Cognitive Impairment Research
- Pulmonary Hypertension Research and Treatments
- Pancreatic function and diabetes
- Mechanical Circulatory Support Devices
- Coronary Interventions and Diagnostics
- Diabetes and associated disorders
- Diabetes Treatment and Management
- Cardiovascular Health and Disease Prevention
- Cardiac Valve Diseases and Treatments
- Cancer-related gene regulation
- Sulfur Compounds in Biology
- Ion Transport and Channel Regulation
- Cerebrovascular and Carotid Artery Diseases
- Hydrogen's biological and therapeutic effects
- Phosphodiesterase function and regulation
University of North Carolina at Chapel Hill
2023-2024
University of North Carolina Health Care
2024
Augusta University
2014-2023
Augusta University Health
2019-2021
Abstract Aims Sodium-glucose-cotransporter-2 inhibitors showed favourable cardiovascular outcomes, but the underlying mechanisms are still elusive. This study investigated of empagliflozin in human and murine heart failure with preserved ejection fraction (HFpEF). Methods results The acute were myocardium from patients HFpEF ZDF obese rats, which treated vivo. As shown immunoblots ELISA, significantly suppressed increased levels ICAM-1, VCAM-1, TNF-α, IL-6 attenuated pathological oxidative...
Abstract Glycan-binding proteins (GBPs) play critical roles in diverse cellular functions such as cell adhesion, signal transduction and immune response. Studies of the interaction between GBPs glycans have been hampered by availability high throughput high-content technologies. Here we report multiplex glycan bead array (MGBA) that allows simultaneous analyses 384 samples up to 500 a single assay. The specificity, sensitivity reproducibility MGBA are evaluated using 39 plant lectins, 13...
Background: Heart failure with preserved ejection fraction (HFpEF) is often manifested as impaired cardiovascular reserve. We sought to determine if conducted vasodilation, which coordinates microvascular resistance longitudinally match tissue metabolic demand, becomes compromised in HFpEF. hypothesized that the vasodilator adenosine facilitates and inhibition of ADK (adenosine kinase) augments vasodilation for a more efficient myocardial perfusion improved left ventricle (LV) diastolic...
Introduction The disintegrin and metalloproteinase 17 (ADAM17) exhibits α-secretase activity, whereby it can prevent the production of neurotoxic amyloid precursor protein-α (APP). ADAM17 is abundantly expressed in vascular endothelial cells may act to regulate homeostatic responses, including vasomotor function, wall morphology, formation new blood vessels. role neurodegenerative diseases remains poorly understood. Here, we hypothesized that cerebrovascular plays a pathogenesis Alzheimer’s...
In type 2 diabetes (T2D) microvascular dysfunction can interfere with tissue glucose uptake thereby contributing to the development of hyperglycemia. The cell membrane caveolae orchestrate signaling pathways that include control perfusion. this study, we examined role in regulation vasomotor function under condition hyperglycemia T2D patients and rodent models. Human coronary arterioles were obtained during cardiac surgery from patients, higher perioperative levels, normoglycemic,...
Inhibition of adenosine kinase (ADK), via augmenting endogenous levels exerts cardiovascular protection. We tested the hypothesis that ADK inhibition improves microvascular dilator and left ventricle (LV) contractile function under metabolic or hemodynamic stress.In Obese diabetic Zucker fatty/spontaneously hypertensive heart failure F1 hybrid rats, treatment with selective inhibitor, ABT-702 (1.5 mg/kg, intraperitoneal injections for 8-week) restored acetylcholine-, sodium nitroprusside-,...
The disintegrin and metalloproteinase 17 (ADAM17) exhibits α-secretase activity, whereby it can prevent the production of neurotoxic amyloid precursor protein-α (APP). ADAM17 is abundantly expressed in vascular endothelial cells may act to regulate homeostatic responses, including growth vasomotor function. We hypothesized that cerebrovascular plays a role pathogenesis Alzheimer’s disease (AD). Here we found 8-10 months old APP/PS1 mice (expressing transgenes for APP Swedish mutation PSEN1...
Lymphatic dysfunction can lead to fetal loss due interstitial edema known as hydrops fetalis during development and lymphedema in adulthood. Lymphedema affects an estimated 250 million individuals worldwide, yet there is no effective treatment available. Numerous studies have established G protein-coupled receptors (GPCRs) key lymphangiogenic signaling pathways ideal druggable therapeutical targets. β-arrestins (β-arrestin 1 2) are ubiquitously expressed cytosolic adaptor proteins which...
Lymphatic vessels of the heart undergo dynamic remodeling in response to physiological and pathological cardiovascular events such as development, adult cardiac maintenance injury repair. During pregnancy, system undergoes changes meet increased demand blood supply fetus. These extensive physiologic make pregnancy delivery a high-risk period woman's life. However, whether how lymphatics change during is largely undefined. Therefore, we used whole mount immunofluorescent labeling quantitative...
Coronary microvascular dysfunction (CMD) develops in patients with heart failure preserved ejection fraction (HFpEF, also known as diastolic failure), but the nature of underlying pathomechanisms behind this prevalent disease remain poorly understood. The hypothesis tested was that coronary rarefaction contributes to left ventricle (LV) function HFpEF. obese ZSF1 rat model human HFpEF employed and using transthoracic echocardiography it found 18-week-old male rats exhibited a significantly...
Microvascular vasodilator dysfunction frequently accompanies myocardial contractile dysfunction, but the mechanistic interrelationship between these pathologies remains poorly understood, and hence therapeutic interventions are limited. We sought to determine if vascular endothelium selective inhibition of adenosine kinase (ADK), major metabolizing enzyme, augments vasodilation improves pressure‐overload induced left ventricle (LV) systolic diastolic dysfunction. Mice with...
Coronary microvascular dysfunction develops in patients with heart failure preserved ejection fraction (HFpEF, also known as diastolic failure). Phosphodiesterase 9A (PDE9A) was shown to be upregulated the hypertrophic myocardium HFpEF patients. The hypothesis tested that PDE9A inhibition improves coronary arteriole vasodilation and left ventricle (LV) function HFpEF. obese ZSF1 rat, a model of human HFpEF, employed which it found LV by 20 weeks age. 18‐week old male ZSF‐1 rats were treated...
Expansion of pericardial adipose tissue ( p AT) correlates with the severity coronary artery disease in obese patients. Dysfunctional AT is a significant source pro‐inflammatory cytokine and adipokine production, but mechanisms that underlie dysfunction remain poorly understood. During angiogenesis vascular endothelial growth factor (VEGF) activates A disintegrin metalloproteinase ADAM17 induce Notch ectodomain shedding to promote new vessel growth. We hypothesized ADAM17‐mediated...
We sought to determine if lumen narrowing inward arterial remodeling is mediated by impaired endothelial mechanosensing of wall shear stress (WSS) in aging. Previously we have shown that aging upregulates A disintegrin and metalloproteinase ADAM17 the vascular endothelium. sheds F11R/JAM‐A, an important tight junction‐located cell (EC) adhesion molecule. Here tested activation promotes aging‐related artery shedding F11R/JAM‐A. Human arteries were obtained from fat biopsies 40 consecutive...
Coronary microvascular dysfunction contributes to the development of heart failure with preserved ejection fraction (HFpEF) for which no effective therapies are currently available. We tested hypothesis that pharmacological inhibition adenosine kinase (ADK), major metabolizing enzyme, augments coronary artery vasodilation and improves left ventricle (LV) diastolic function in HFpEF. employed obese ZSF1 rat model assessed agonist‐induced dilation performed echocardiographic assessment LV...
Junctional Adhesion Molecule A (F11R/JAM‐A), which can be shed by a disintegrin and metalloproteinase ADAM17, has been implicated in arterial mechanotransduction. We hypothesized that aging ADAM17 activation impairs wall shear stress mechanosensing via an augmented F11R/JAM‐A shedding. Using videomicroscopy we found reduced (WSS)‐induced dilation isolated, pressurized gracilis muscle arteries 30‐month old (aged) mice, when compared to 12‐week (young) controls. Dilations acetylcholine or the...
Pulmonary complications are common in patients with diastolic heart failure, also known as failure preserved ejection fraction (HFpEF). We tested the hypothesis that pulmonary microvascular dysfunction develops HFpEF. employed two different rodent models of HFpEF, uninephrectomized and DOCA (UNX‐DOCA) salt treated rats well aldosterone (UNX‐Aldo) infused mice. Left ventricle (LV) function was assessed by transthoracic echocardiography (E/A ratio deceleration time). Microvascular vasodilator...
The Endothelial Cell-Selective Adhesion Molecule (ESAM) mediates inflammatory cell transmigration and also involved in pathological angiogenesis. Here we investigated the role of ESAM affecting vasodilator cardiac contractile function. To that end knockout wild type (WT) mice were employed. Using transthoracic echocardiography it was found displayed left ventricle (LV) diastolic dysfunction, as indicated by a significantly reduced E/A ratio (E=early, A=late mitral inflow peak velocities),...
CD44 is differentially spliced to form specific variants, but little known regarding their contribution cardiovascular pathologies. Specifically, variant 6 (CD44v6) involved in abnormal angiogenesis. The hypothesis tested was that CD44v6 leads coronary microvascular rarefaction whereby it contributes left ventricle (LV) diastolic function heart failure with preserved ejection fraction (HFpEF, also as failure). obese ZSF1 rat model of human HFpEF employed and using transthoracic...
The disintegrin and metalloproteinase 17 (ADAM17), abundantly expressed in cerebrovascular endothelial cells, is one of the important α-secretases involved cleavage amyloid precursor protein-α (APP). We hypothesized that abnormal function vascular ADAM17 contributes to cognitive impairment Alzheimer's disease (AD). used 8-10 months old male female wild type APP/PS1 mice containing human transgenes for both APP bearing Swedish mutation PSEN1 an L166P mutation. found expression brain...