TY - JOUR
T1 - Development of Rho-kinase inhibitors for cardiovascular medicine
AU - Shimokawa, Hiroaki
AU - Rashid, Mamunur
N1 - Funding Information:
Our work presented here was supported in part by grants in aid (08557050, 09281225, 09470169, 10177223, 10357006, 12032215, 12470158, 12877114, 13307024, 13557068, 15256003 and 16209027) from the Japanese Ministry of Education, Culture, Sports, Science and Technology, the Program for Promotion of Fundamental Studies in Health Sciences of the Organization for Pharmaceutical Safety and Research of Japan, and CREST. We thank coworkers at the Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences and at the Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine. We also thank K. Kaibuchi and M. Amano at the Department of Cell Pharmacology and Asahi Kasei Pharma for their cooperation in our studies.
PY - 2007/6
Y1 - 2007/6
N2 - Rho-kinase (ROCK) is one of the downstream effectors of the small G-protein Rho. The Rho-ROCK pathway has an important role in mediating various cellular functions, including contraction, actin cytoskeleton organization, cell adhesion and motility, proliferation, cytokinesis and gene expression, all of which are involved in the pathogenesis of cardiovascular disease. Indeed, vascular smooth muscle cells, endothelial cells, adventitial cells, cardiomyocytes and nerve cells all undergo pathophysiological changes through the ROCK pathway. Abnormal activation of this pathway is associated with the pathogenesis of various cardiovascular diseases such as hypertension, coronary and cerebral vasospasm, restenosis, atherosclerosis, stroke and heart failure, although the roles of the ROCK isoforms (ROCK1 and ROCK2) remain to be elucidated. In this article, we review the information about the therapeutic importance of the ROCK pathway and summarize the current status of the development of ROCK inhibitors.
AB - Rho-kinase (ROCK) is one of the downstream effectors of the small G-protein Rho. The Rho-ROCK pathway has an important role in mediating various cellular functions, including contraction, actin cytoskeleton organization, cell adhesion and motility, proliferation, cytokinesis and gene expression, all of which are involved in the pathogenesis of cardiovascular disease. Indeed, vascular smooth muscle cells, endothelial cells, adventitial cells, cardiomyocytes and nerve cells all undergo pathophysiological changes through the ROCK pathway. Abnormal activation of this pathway is associated with the pathogenesis of various cardiovascular diseases such as hypertension, coronary and cerebral vasospasm, restenosis, atherosclerosis, stroke and heart failure, although the roles of the ROCK isoforms (ROCK1 and ROCK2) remain to be elucidated. In this article, we review the information about the therapeutic importance of the ROCK pathway and summarize the current status of the development of ROCK inhibitors.
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U2 - 10.1016/j.tips.2007.04.006
DO - 10.1016/j.tips.2007.04.006
M3 - Review article
C2 - 17482681
AN - SCOPUS:34249301303
VL - 28
SP - 296
EP - 302
JO - Trends in Pharmacological Sciences
JF - Trends in Pharmacological Sciences
SN - 0165-6147
IS - 6
ER -