Rho Kinase Inhibitors: Potential Treatments for Diabetes and Diabetic Complications

被引：48

作者：

Zhou, Hong ^{[2
]}

Li, Yong-jun ^{[1
]}

机构：

[1] Hebei Med Univ, Hosp 2, Dept Cardiol, Shijiazhuang 050000, Peoples R China

[2] Hebei Med Univ, Hosp 2, Dept Endocrinol, Shijiazhuang 050000, Peoples R China

来源：

CURRENT PHARMACEUTICAL DESIGN | 2012年 / 18卷 / 20期

关键词：

RhoA; Rho kinase; inhibitors; diabetes; complications; SMOOTH-MUSCLE-CELLS; PROLIFERATIVE VITREORETINAL DISEASES; UNILATERAL URETERAL OBSTRUCTION; FASUDIL HYDROCHLORIDE HYDRATE; CARDIAC MYOCYTE APOPTOSIS; CORONARY-ARTERY SPASM; NITRIC-OXIDE SYNTHASE; BINDING PROTEIN RHO; RHO/RHO-KINASE; ENDOTHELIAL-CELLS;

D O I：

10.2174/138161212800672688

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

The small GTPase RhoA and its downstream effector, Rho kinase (ROCK), appear to mediate numerous pathophysiological signals, including smooth muscle cell contraction, actin cytoskeleton organization, cell adhesion and motility, proliferation, differentiation and the expression of several genes. Clinical interest in the RhoA/ROCK pathway has increased, due to emerging evidence that this signaling pathway is involved in the pathogenesis of several diseases, including hypertension, coronary vasospasm, stroke, atherosclerosis, heart failure and diabetes; ROCK is considered an important future therapeutic target. Several pharmaceutical companies are already actively engaged in the development of ROCK inhibitors as the next generation of therapeutic agents for these diseases. This review discusses the relationship between diabetes and hyperglycemia-induced RhoA/ROCK activation, highlights recent findings on the roles of ROCK inhibitors from experimental models of diabetes and clinical studies in cardiovascular patients, and elucidates major challenges for developing more selective ROCK inhibitors. Accumulating evidence suggests the potential of ROCK inhibitors as therapeutic agents for diabetes and its complications.

引用

页码：2964 / 2973

页数：10

共 146 条

[1]

High glucose-induced upregulation of Rho/Rho-kinase via platelet-derived growth factor receptor-β increases migration of aortic smooth muscle cells [J].