Searching for the physiological role and therapeutic potential of vascular proteinase-activated receptor-2 (PAR2)
Diabetes Mellitus, Type 2
The intercellular interactions of endothelial and vascular smooth muscle cells are interesting to many scientists who seek to develop new drugs to treat cardiovascular diseases. Of particular interest is the regulation of blood flow by the paracrine actions of the endothelium on the underlying vascular smooth muscle cells of blood vessels. The development and further understanding of drugs that mimic or potentiate endothelial-derived factors, in particular vasodilators such as nitric oxide (NO), have proved to be of therapeutic benefit (e.g., sildenafil, nitroglycerin). On the other hand, endothelial-derived proinflammatory substances are released in response to tissue insult or during the progression of vascular diseases such as atherosclerosis. Proteinase-activated receptor 2 (PAR2) represents a novel target for vascular biology because of 1) its unique mechanism of activation by proteinases, 2) questions regarding the identity of the endogenous agonist(s), and 3) its apparent multiple activities in the vasculature. Whether it will be agonists or antagonists of PAR2 that will serve as the basis for a new class of therapeutic agents for the treatment of vascular diseases is an open question for further research and drug development. © 2003 Wiley-Liss, Inc.
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