Department of Pharmacology
Basic Science Building, Rm. 533
15 Dana Road
Valhalla, NY 10595
Our research explores the role of the vasoactive cytochrome P450 (CYP)-derived eicosanoid, 20-hydroxyeicosatetraenoic acid (20-HETE) across the vasculature with a focus on endothelial and vascular smooth muscle signaling. Recently, our lab identified the orphan receptor GPR75 as a specific cellular target of 20-HETE through the use of a variety of novel compounds and techniques including crosslinking analogs, click-chemistry, proteomic, binding and functional assays. Through our collaborations across various fields we have illustrated a direct relationship between the production of 20-HETE and blood pressure in animal models of hypertension. Our work has shown 20-HETE to be a potent inducer of endothelial angiotensin converting enzyme (ACE) expression and activity through a EGFR-/MAPK-/IKK-/NF-kB- dependent signaling mechanism. Increased vascular synthesis of 20-HETE in vivo was shown to also be associated with increased ACE expression, circulating angiotensin II (Ang II) levels, blood pressure elevations and vascular remodeling. These changes are prevented or reversed by 20-HETE antagonists. Our research goals include exploring the 20-HETE-GPR75 pairing and its contribution in reducing nitric oxide (NO) bioavailability, increases in inflammatory cytokine production and the induction of ACE expression and activity. The knowledge gained from our continued pursuits will allow us to better understand the mechanisms governing vascular dysfunction, hypertension and cardiovascular disease.