Published online before print November 9, 2006, doi: 10.1161/01.ATV.0000251995.73307.2d
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© 2007 American Heart Association, Inc.
Brief Reviews |
The Roles of Proteinase-Activated Receptors in the Vascular Physiology and Pathophysiology
From the Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Correspondence to Katsuya Hirano, MD, PhD, Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail khirano{at}molcar.med.kyushu-u.ac.jp
Proteinase-activated receptors (PARs) belong to a family of G protein–coupled receptors, thus mediating the cellular effects of proteinases. In the vascular system, thrombin and other proteinases in the coagulation-fibrinolysis system are considered to be the physiologically relevant agonists, whereas PARs are among the most important mechanisms mediating the interaction between the coagulation–fibrinolysis system and the vascular wall. Under physiological conditions, PARs are mainly expressed in endothelial cells, and participate in the regulation of vascular tone, mostly by inducing endothelium-dependent relaxation. PARs in endothelial cells are also suggested to contribute to a proinflammatory phenotypic conversion and an increase in the permeability of vascular lesions. In smooth muscle cells, PARs mediate contraction, migration, proliferation, hypertrophy, and production of the extracellular matrix, thereby contributing to the development of vascular lesions and the pathophysiology of such vascular diseases as atherosclerosis. However, the expression of PARs in the smooth muscle of normal arteries is limited. The upregulation of PARs in the smooth muscle is thus considered to be a key step for PARs to participate in the pathogenesis of vascular lesions. Elucidating the molecular mechanism regulating the PARs expression is therefore important to develop new strategies for the prevention and treatment of vascular diseases.
Proteinase-activated receptors (PARs) play critical roles in vascular physiology and pathophysiology. The receptor upregulation is considered to be a key step in contributing to vascular lesion development and pathophysiology of vascular diseases. Elucidating the molecular mechanism regulating PARs expression is thus the next important step in PARs research.
Key Words: thrombin • receptors • vascular biology • endothelium • smooth muscle
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