Researchers find new proteins that regulate blood pressure, flow

July 7, 2010, University of Pittsburgh Schools of the Health Sciences

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 could lead to a better understanding of who will get 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 , stroke and ."

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 (NO) signaling. The cells that line , 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 told us TSP1 could alter NO signaling. But TSP1 is a protein too large to cross through the endothelial layer and into the blood vessel wall, so it was not obvious how it could alter the muscle tone of the arteries," Dr. Isenberg said. "We also knew that mice genetically engineered to not produce TSP1 or CD47 showed more NO-based blood flow and blood vessel dilation. This suggested to us that perhaps circulating TSP1 was altering the ability of the endothelium to make NO by acting on eNOS."

He and his team are now developing agents that can alter the activity of eNOS by "blocking" the inhibitory signal mediated by TSP1 and CD47, which have the potential to be novel blood pressure-regulating drugs. Some cases of hypertension may arise from gene-based differences in these proteins, Dr. Isenberg noted.

"This work has identified a key pathway that effectively puts the brakes on nitric oxide production, which slows down blood flow," said Mark T. Gladwin, M.D., director of the Vascular Medicine Institute. "Furthermore, drugs that block this pathway have the potential to restore nitric oxide levels and may be useful for the treatment of high blood pressure and other vascular diseases."

Related Stories

Recommended for you

Democratizing science: Researchers make neuroscience experiments easier to share, reproduce

March 16, 2018
Over the past few years, scientists have faced a problem: They often cannot reproduce the results of experiments done by themselves or their peers.

Human 'chimeric' cells restore crucial protein in Duchenne muscular dystrophy

March 16, 2018
Cells made by fusing a normal human muscle cell with a muscle cell from a person with Duchenne muscular dystrophy —a rare but fatal form of muscular dystrophy—were able to significantly improve muscle function when implanted ...

Team develops 3-D tissue model of a developing human heart

March 16, 2018
The heart is the first organ to develop in the womb and the first cause of concern for many parents.

Genetic variant discovery to help asthma sufferers

March 16, 2018
Research from the University of Liverpool, published today in Lancet Respiratory Medicine, identifies a genetic variant that could improve the safety and effectiveness of corticosteroids, drugs that are used to treat a range ...

Researchers say use of artificial intelligence in medicine raises ethical questions

March 15, 2018
In a perspective piece, Stanford researchers discuss the ethical implications of using machine-learning tools in making health care decisions for patients.

Study identifies potential drug for treatment of debilitating inherited neurological disease

March 15, 2018
St. Jude Children's Research Hospital scientists have demonstrated in mouse studies that the neurological disease spinal bulbar muscular atrophy (SBMA) can be successfully treated with drugs. The finding paves the way for ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.