Rho kinase inhibitors: potential treatments for diabetes and diabetic complications

Current Pharmaceutical Design
Hong Zhou, Yong-jun Li

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.

Citations

Aug 8, 2013·Journal of Cardiovascular Pharmacology·Jianjian Shi, Lei Wei
Apr 9, 2014·PloS One·Kristine H KurtzJerome W Breslin
Oct 17, 2013·International Journal of Molecular Sciences·Hongping YinCuiqing Liu
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Oct 12, 2016·BMC Cardiovascular Disorders·Zhijun SunHongwei Li
Aug 21, 2013·Biological Chemistry·Ehsan AminMohammad R Ahmadian
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Feb 12, 2017·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Yahor TratsiakovichJohn Pernow

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