Title:Rho Kinase Inhibitors: Potential Treatments for Diabetes and Diabetic Complications
Volume: 18
Issue: 20
Author(s): Hong Zhou and Yong-jun Li
Affiliation:
Keywords:
RhoA, Rho kinase, inhibitors, diabetes, complications, GTPase, hypertension, coronary vasospasm, stroke, atherosclerosis
Abstract: 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.
