The overall emphasis of Dr. David X. Zhang's research is to understand the cellular mechanisms by which the endothelium regulates blood vessel tone in both normal physiological conditions and disease states, such as ischemic heart disease and hypertension.
The endothelium is a single layer of vascular cells lining the lumen of blood vessels; it regulates vascular tone through the release of vasoactive mediators in response to either chemical or mechanical stimuli. Some of these mediators include nitric oxide (NO), prostacyclin, and less well-understood endothelium-derived hyperpolarizing factors such as metabolites of arachidonic acid and reactive oxygen species (e.g. hydrogen peroxide). Of particular interest to our group are the identities and mechanisms of action of endothelial relaxing factors in the coronary microcirculation in humans with or without underlying vascular disorders (e.g. coronary artery disease). These studies are important to our understanding of the pathogenesis of vascular diseases and may reveal new therapeutic targets for the treatment of these diseases. Studies are performed with an integrated approach incorporating molecular biology (RT-PCR, Western blot, RNAi and genetic knockout), cell biology (confocal microscopy, protein over-expression in cell lines and vascular cells), electrophysiology, and fluorescence imaging techniques (Ca2+ assay, membrane potential measurement) with isolated vessel reactivity assay (videomicroscopy, wire myograph).
His current research focus is to determine how blood flow stimulates vascular endothelial cells to release relaxing factors that in turn cause vessel relaxation, a phenomenon termed as flow-mediated dilation. In particular, we examine whether the transient receptor potential vanilloid 4 (TRPV4) channel, a cation channel of the TRP channel superfamily expressed in endothelial cells of various species and vascular beds, is activated by flow and whether this activation results in a cascade of cellular events leading to vessel relaxation. The studies are clinically significant because they involve the use of both human tissue and animal models.