Rho-associated coiled-coil-forming kinases (ROCKs): potential targets for the treatment of atherosclerosis and vascular disease

Trends Pharmacol Sci. 2011 Mar;32(3):167-73. doi: 10.1016/j.tips.2010.12.006. Epub 2011 Jan 16.

Abstract

ROCKs are important regulators of the actin cytoskeleton. Because changes in the actin cytoskeleton underlie vascular contractility and remodeling, inflammatory cell recruitment, and cell proliferation, it is likely that the Rho/ROCK pathway will play a central role in mediating vascular function. Indeed, increased ROCK activity is observed in cerebral and coronary vasospasm, hypertension, vascular inflammation, arteriosclerosis, and atherosclerosis. Recent experimental and clinical studies suggest that inhibition of ROCK could be a promising target for the treatment of cardiovascular disease. For example, inhibition of ROCK might be the underlying mechanism by which statins or HMG-CoA reductase inhibitors exert their therapeutic benefits beyond cholesterol reduction. In this review we summarize current understanding of the crucial role of RhoA/ROCK pathway in the regulation of vascular function and discuss its therapeutic potential in the treatment of atherosclerosis and vascular disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / physiopathology
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / physiopathology
  • Drug Delivery Systems
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / pharmacology
  • Vascular Diseases / drug therapy*
  • Vascular Diseases / physiopathology
  • rho-Associated Kinases / antagonists & inhibitors*
  • rho-Associated Kinases / metabolism

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Protein Kinase Inhibitors
  • rho-Associated Kinases