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Pitt researchers find new proteins that regulate blood pressure, flow
Date:7/7/2010

PITTSBURGH, July 7 Researchers at the University of Pittsburgh School of Medicine have identified key players in a little-known biochemical pathway that appears to regulate blood pressure. The findings, reported in the early online version of Cardiovascular Research, have evolved from studies conducted by Jeffrey S. Isenberg, M.D., Eileen M. Bauer, Ph.D., and their colleagues at Pitt's Vascular Medicine Institute.

"Identifying and unraveling this important pathway for blood pressure regulation could lead to a better understanding of who will get high blood pressure and why, as well as allow us to develop better drugs to treat these patients," Dr. Isenberg said. "Poorly controlled hypertension is a major risk factor for heart attacks and heart failure, stroke and kidney failure."

The pathway he and collaborator David D. Roberts, Ph.D., of the National Cancer Institute (NCI), National Institutes of Health (NIH), have been exploring involves nitric oxide (NO) signaling. The cells that line blood vessels, called the endothelium, produce NO in a few biochemical steps. NO promotes blood vessel dilation and increases blood flow. Conversely, endothelial dysfunction, along with loss of NO production, is known to be involved in the development of many forms of cardiovascular disease, including hypertension.

Through cell culture and mouse experiments, the researchers found that a protein called thrombospondin-1 (TSP1) and its receptor, CD47, inhibit activation of the endothelial-based enzyme called endothelial nitric oxide synthase (eNOS), which in turn limits the production of NO and thus prevents blood vessels from relaxing and blood pressure from dropping. Circulating TSP1, at levels consistent with those found in the blood stream, is capable of inhibiting activation of endothelial-based eNOS and thus blocking NO production.

"For some time now, it has not been clear what role TSP1 served in the blood. Experiments in cells to
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Contact: Anita Srikameswaran
SrikamAV@upmc.edu
412-578-9193
University of Pittsburgh Schools of the Health Sciences
Source:Eurekalert

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