US EPA

1574349 

Journal Article 

Rho Kinase Inhibitors: Potential Treatments for Diabetes and Diabetic Complications 

Zhou, H; Li, Y 

2012 

Yes 

Current Pharmaceutical Design
ISSN: 1381-6128
EISSN: 1873-4286 

18 

20 

2964-2973 

22571664 

WOS:000306547500012 

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. 

RhoA; Rho kinase; inhibitors; diabetes; complications