Oxygen free radical, release in human failing myocardium is associated with increased activity of Rac1-GTPase and represents a target for statin treatment

  • Maack C
  • Kartes T
  • Kilter H
 et al. 
  • 48

    Readers

    Mendeley users who have this article in their library.
  • 302

    Citations

    Citations of this article.

Abstract

BACKGROUND: Reactive oxygen species (ROS) contribute to the development of heart failure. A potential source of myocardial ROS is the NADPH oxidase, which is regulated by the small GTP-binding protein rac1. Isoprenylation of rac1 can be inhibited by statin therapy. Thus, we examined ROS and rac1 in human failing myocardium and tested their regulation by statins in vivo.

METHODS AND RESULTS: In human left ventricular myocardium from patients with ischemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM), NADPH oxidase activity was increased 1.5-fold compared with nonfailing controls (P
CONCLUSIONS: Failing myocardium of patients with DCM and ICM is characterized by upregulation of NADPH oxidase-mediated ROS release associated with increased rac1 activity. Oral statin treatment inhibits myocardial rac1-GTPase activity. These data suggest that extrahepatic effects of statins can be observed in humans and may be beneficial for patients with chronic heart failure.

Author-supplied keywords

  • Free radicals
  • Heart failure
  • Inhibitors
  • Myocardium
  • Statins

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free