Role of protease-activated receptors in the vascular system.
Thrombin is one of the key molecules involved in the development of vascular diseases. Thrombin does not only serve as a coagulation factor, but it also exerts cellular effects by activating protease (proteinase)-activated receptors (PARs), a family of seven-transmembrane G protein-coupled receptors. This study focused on the role of PARs in the vascular system. Among the four members so far identified, PAR-1 and PAR-2 were found to play an important role in the vascular system, while the functional roles of PAR-3 and PAR-4 appear to be mostly limited to platelets. The endothelial cells play a primary role in mediating the vascular effects of PARs under physiological conditions, while PARs of the smooth muscle cells can be induced under pathological conditions, and therefore play a more pathophysiological role. PAR-1 and PAR-2 mediate various vascular effects including regulation of vascular tone, proliferation and hypertrophy of smooth muscle and angiogenesis. Since proteases are activated under pathological conditions such as hemorrhage, tissue damage, and inflammation, PARs are suggested to play a critical role in the development of functional and structural abnormality in the vascular lesion. Understanding the functional role of PARs in the vascular system can thus help in the development of new strategies for the prevention and therapy of vascular diseases.
Hirano
Katsuya
K
Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kanaide
Hideo
H
D001161:Arteriosclerosis / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D044463:Receptor, PAR-1 / Q000502:physiology; D044464:Receptor, PAR-2 / Q000502:physiology; D044462:Receptors, Proteinase-Activated / Q000502:physiology*; D018179:Receptors, Thrombin / Q000502:physiology; D013917:Thrombin / Q000502:physiology*
D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D044462:Receptors, Proteinase-Activated; D018179:Receptors, Thrombin; C105295:protease-activated receptor 3; D013917:Thrombin; C112908:protease-activated receptor 4