Does it matter whether or not a lipid-lowering agent inhibits Rho kinase?

Curr Atheroscler Rep. 2007 Nov;9(5):384-8. doi: 10.1007/s11883-007-0049-9.

Abstract

Lipid-lowering agents, such as 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, also known as statins, have been shown to reduce cardiovascular events. However, evidence from recent clinical trials suggests that some of the beneficial effects of statins may be unrelated to changes in low-density lipoprotein cholesterol. In animal studies, many of the cholesterol-independent or "pleiotropic" effects of statins are mediated by inhibition of Rho kinase (ROCK). Indeed, ROCK has been implicated in the regulation of vascular tone, proliferation, inflammation, and oxidative stress. To what extent ROCK activity is inhibited in patients on lipid-lowering therapy, and in particular on statins, is not known, but it may have important clinical and therapeutic implications. This review attempts to make the case that, in addition to lipid lowering, inhibition of ROCK contributes to some of the benefits of statin therapy in patients with cardiovascular disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / physiopathology
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Oxidative Stress / drug effects
  • rho-Associated Kinases / antagonists & inhibitors*

Substances

  • Enzyme Inhibitors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • rho-Associated Kinases