"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."
Source-Eurekalert