Authors: Zhou, Qian; Liao, James K.

Source: Current Pharmaceutical Design, Volume 15, Number 27, September 2009 , pp. 3108-3115(8)

Publisher: Bentham Science Publishers

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

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138161209789057986

Affiliations: 1: Vascular Medicine Research Unit, Brigham and Women's Hospital and Harvard Medical School, 65 Landsdowne Street, Room 275, Cambridge, MA 02139, USA.

Publication date: 2009-09-01

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• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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