title: Simvastatin attenuated cerebrovascular cell proliferation in the development of hypertension through Rho/Rho-kinase pathway.
abstract: The cerebrovascular remodeling is a prominent feature of hypertension and considered as a major risk of stroke. Statins may suppress the activation of the Rho/Rho-kinase pathway and have pleiotropic actions against the development of vascular remodeling. We hypothesized that the inhibition of the Rho/Rho-kinase pathway by simvastatin during hypertension could recuperate the pathological changes of basilar artery through the downregulation of cell proliferation. To resolve the problem, we used 2-kid, 2-clip rat as a hypertension model and evaluated the effect of simvastatin on the Rho/Rho-kinase pathway. In addition, we assessed the changes of the proliferation rate by CCK-8 assay in basilar artery smooth muscle cells. Our results from this study showed that a continuous increase in the plasma endothelin-1 (ET-1) concentration and the Rho/Rho-kinase activity was positively correlated with changes in blood pressure in the hypertensive rat. Simvastatin ameliorated the upregulated Rho/Rho-kinase activity and cell proliferation during hypertension. Moreover, simvastatin, the RhoA inhibitor C3, and the RhoA-kinase inhibitor Y27632 all attenuated the proliferation rate induced by ET-1 in basilar artery smooth muscle cells via the Rho/Rho-kinase signaling pathway. In conclusion, simvastatin attenuated ET-1-induced proliferation through the Rho/Rho-kinase signaling pathway in hypertensive rat basilar artery, and it may be an excellent reagent to protect vascular remodeling and stroke.
authors.affiliation: Department of Pharmacology, Cardiac and Cerebrovascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Ma
authors.forename: Shi-Yang
authors.initials: SY
authors.lastname: Li
authors.forename: Mi
authors.initials: M
authors.lastname: Wang
authors.forename: Yong-Yuan
authors.initials: YY
authors.lastname: Guan
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000097:blood; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D019821:Simvastatin / Q000494:pharmacology*; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000577:Amides; D019332:Endothelin-1; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; C108830:Y 27632; D019821:Simvastatin; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein