The Cardiovascular Research Group in the Department of Pharmacology and Toxicology mainly focus on 4 scientific topics: 1) Atherogenesis. There are several research projects that deal with the pathogenesis of atherosclerosis and related novel therapeutic strategies. We are testing whether a CD38-ADP-ribosyslcyclase signaling pathway controls the autophagic process in coronary arterial smooth muscle cells (CASMCs) and thereby protects cells from atherosclerotic injury preventing atherosclerosis. Defect of this signaling pathway may induce or accelerate coronary atherosclerosis during hypercholesterimia. We are also addressing whether a sphingolipid, ceramide serves as a key regulator in the lysosome trafficking that controls autophagic flux protecting CASMCs from atherogenic injury. Another project is to explore the molecular mechanisms mediating the cholesterol transport out of lysosomes to prevent foam cell formation, which is a critical pathological process in atherosclerosis. 2) Hypertension and associated end-stage renal injury. Major focus of our research in this area is on the renal mechanisms of hypertension including the role of renal medullary gene transcriptional regulation via hypoxia-inducible factor-1α (HIF-1α) in the control of blood pressure and the contribution of renal stem cell niche dysfunction to the development of hypertension. We are also investigating whether hyperhomocysteinemia (hHcys) serves as a pathogenic factor independent of elevated arterial pressure to initiate or promote the development of glomerular sclerosis with focus on the triggering mechanisms of NALP3 inflammasome activation, an intracellular inflammatory machinery in podocytes. In addition, a novel renal medullary antihypertensive lipid, that is, prostamide, was identified to have potent antihypertensive action via natriuresis, vasodilation and inhibition of sympathetic activity. 3) Obesity-associated cardiovascular and kidney damage. During obesity, different adipokines such as visfatin are released that lead to cardiovascular and renal injury. Two projects have been developed to explore the mechanisms by which obesity results in endothelial dysfunction and glomerular injury. Inflammasome activation is proposed as a key mechanism responsible for these damages via its inflammatory and non-inflammatory actions. 4) Vascular cell signaling. This project is to elucidate the molecular mechanisms mediating the trafficking of intracellular organelles and molecules to lipid rafts (LR) on cell plasma membrane to conduct transmembrane signaling, which is associated with redox regulation and signalosomes formation. We also identify a novel Ca2+ release channel in lysosomes, namely, a transient receptor potential (TRP) mucolipin 1 (TRP-ML1). This TRP-ML1 channel mediates local Ca2+ bursts from lysosomes and leads to a two-phase Ca2+ release that participates in the regulation of vascular cell functions.
The investigators in Pharmacology and Toxicology interact closely with the cardiovascular research groups within VCU and hold monthly Cardiovascular and Kidney Research Seminar series jointly with other basic science and clinical departments. Please visit the individual faculty sites for further information on Cardiovascular research: