The NYU School of Medicine's Laboratory for Cardiovascular Research in the Department of Medicine uses a multidisciplinary approach to study atherosclerosis from bench to bedside. We focus on the effects of atherogenic biomolecules which modify endothelial function in leukocyte-endothelial interaction, thombosis and fibrinolysis, and endothelial proliferation.
The most compelling theory on the origins of atherosclerosis proposes that atherosclerosis is secondary to endothelial dysfunction or denuding endothelial injury. The mass of atherosclerosis, in turn, is proportional to both the magnitude and persistence of endothelial injury such that factors which delay reendothelialization enhance atherosclerosis. While atherosclerosis accelerates in patients with chronic renal failure (CRF) who are maintained on dialysis, the causes for this acceleration are unknown. We discovered that uremic levels of the end-metabolite oxalic acid dramatically inhibit the proliferation and migration of human endothelial cells (EC) in vitro. Oxalate inhibits endothelial regeneration and is, therefore, a candidate atherogenic toxin. Our recent work links these phenomena to an elevation in intracellular calcium [Ca++]i unique to EC. While it is clear that [Ca++]i is modulated during the cell cycle, it is not clear whether this modulation is both necessary and sufficient for progression through the cell cycle. Thus, the role of [Ca++]i as an oxalate-dependent moderator of EC proliferation is unknown. We are exploring the precise molecular mechanisms by which oxalate increases [Ca++]i, thereby inhibiting reedothelialization and promoting atherogenesis.
Adjunct Professor, Department of Medicine
Professor Emeritus of Medicine, Department of Medicine
Gazing through the crystal ball of science-cardiovascular disease in 2100
US cardiology. 2012; 9(2):86-89
FASEB journal. 2011 Jun; 25(6):1788-1792
Current oncology (Toronto, Ont.). 2011 Jan; 18(1):11-12
American journal of medicine. 2005 Sep; 118(9):1042-1046
The puzzle of aspirin and sex
New England journal of medicine. 2005 Mar 31; 352(13):1366-1368
Journal of the American College of Cardiology. 2004 Aug 04; 44(3):642-643
American journal of cardiology. 2004 May 15; 93(10):1295-1297
Atherosclerosis. 2004 Apr; 173(2):321-328