Endothelial cells line the inner walls of all the arteries, where they release substances that can cause vasodilation and lower the blood pressure. The loss of endothelium-dependent vasodilation increases vascular resistance and blood pressure in cardiovascular disorders. Thus, strategies to target the loss of endothelium-dependent vasodilation may have therapeutic benefit in cardiovascular disorders.
Under normal conditions, endothelium-dependent vasodilation is driven by increases in intracellular calcium. My laboratory studies the activity of individual calcium entry events in endothelial cells and their signaling targets under normal and disease conditions. We focus on two life-threatening disorders that are commonly associated with the loss of endothelial function- obesity and pulmonary hypertension. New findings reveal that calcium influx through TRPV4 ion channels, a key calcium entry pathway in endothelial cells, is drastically reduced in rodent models of obesity or pulmonary hypertension and in human patients. The overarching goal is to rescue TRPV4 ion channel activity in obesity and pulmonary hypertension by specifically targeting the causative mechanisms that lower TRPV4 ion channel activity. Our current studies attempt to improve the interaction between TRPV4 ion channels and their regulatory proteins (AKAP150 in systemic circulation and caveolin-1 in pulmonary circulation) in order to enhance endothelium-dependent vasodilation and decrease vascular resistance.
We use a combination of state-of-the-art techniques to achieve a comprehensive understanding of calcium signaling mechanisms that control vascular resistance, including high-speed confocal imaging of calcium signals, patch clamp electrophysiology to measure ion channel currents, and measurements of arterial diameter and blood pressure coupled with several transgenic mouse models.
For our most current list of publications, please click here.
Robert M. Berne Cardiovascular Research Center (aka CVRC)
Department of Molecular Physiology and Biological Physics
Cardiovascular Training Grant (CVTG and Facebook)