Rho-kinase: important new therapeutic target in cardiovascular diseases

Am J Physiol Heart Circ Physiol. 2011 Aug;301(2):H287-96. doi: 10.1152/ajpheart.00327.2011. Epub 2011 May 27.

Abstract

Rho-kinase (ROCKs) belongs to the family of serine/threonine kinases and is an important downstream effector of the small GTP-binding protein RhoA. There are two isoforms of Rho-kinase, ROCK1 and ROCK2, and they have different functions with ROCK1 for circulating inflammatory cells and ROCK2 for vascular smooth muscle cells. It has been demonstrated that the RhoA/Rho-kinase pathway plays an important role in various fundamental cellular functions, including contraction, motility, proliferation, and apoptosis, leading to the development of cardiovascular disease. The important role of Rho-kinase in vivo has been demonstrated in the pathogenesis of vasospasm, arteriosclerosis, ischemia-reperfusion injury, hypertension, pulmonary hypertension, stroke, and heart failure. Furthermore, the beneficial effects of fasudil, a selective Rho-kinase inhibitor, have been demonstrated for the treatment of several cardiovascular diseases in humans. Thus the Rho-kinase pathway is an important new therapeutic target in cardiovascular medicine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood Vessels / drug effects*
  • Blood Vessels / enzymology
  • Blood Vessels / physiopathology
  • Cardiovascular Agents / therapeutic use*
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / enzymology
  • Cardiovascular Diseases / physiopathology
  • Humans
  • Inflammation Mediators / metabolism
  • Molecular Targeted Therapy*
  • Myocardium / enzymology*
  • Oxidative Stress / drug effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Signal Transduction / drug effects
  • rho-Associated Kinases / antagonists & inhibitors*
  • rho-Associated Kinases / metabolism

Substances

  • Cardiovascular Agents
  • Inflammation Mediators
  • Protein Kinase Inhibitors
  • rho-Associated Kinases