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Current Pharmaceutical Design

Eiditor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Rho Kinase: An Important Mediator of Atherosclerosis and Vascular Disease

Author(s): Qian Zhou and James K. Liao

Volume 15 , Issue 27 , 2009

Page: [3108 - 3115] Pages: 8

DOI: 10.2174/138161209789057986

Price: $58

Abstract

Atherosclerosis is a complex inflammatory process characterized by the cross-talk between excessive inflammation and lipid accumulation. In the past few years, compelling evidence suggests that statins can decrease vascular inflammation and attenuate the development of atherosclerosis through their so-called “pleiotropic effects”. These cholesterol-independent effects are predominantly due to their ability to inhibit isoprenoid synthesis. In particular, inhibition of geranylgeranylpyrophosphate synthesis leads to inhibition of Rho and its downstream target, Rho-kinase (ROCK). Thus, one of the beneficial effects of statin therapy could be due to inhibitory effects on ROCK. ROCK is involved in mediating diverse cellular functions such as smooth muscle contraction, cell migration and proliferation. While increased ROCK activity is associated with endothelial dysfunction, cerebral ischemia, coronary vasospasms and metabolic syndrome, the inhibition of ROCK by statins or selective ROCK inhibitors leads to up-regulation of endothelial nitric oxide synthase (eNOS), decreased vascular inflammation, and reduced atherosclerotic plaque formation. This review will focus on the impact of ROCK in cardiovascular disease and its contributory role to vascular inflammation and the atherosclerosis.

Keywords: Rho-kinase, inflammation, atherosclerosis, statin


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