Atorvastatin improves cardiac function of rats with chronic cardiac failure via inhibiting Rac1/P47phox/P67phox-mediated ROS release

Eur Rev Med Pharmacol Sci. 2015 Oct;19(20):3940-6.

Abstract

Objective: To discuss the protective mechanisms of atorvastatin treatment for isoproterenol (ISO)-induced chronic heart failure.

Materials and methods: The rats were randomly divided into three groups: normal group (n = 15, age-matched normal adult rats), ISO group (n = 11, ISO induced heart failure) and atorvastatin group (n = 14, ISO induced lesion but received atorvastatin treatment). The cardiac function was evaluated by echocardiography and hemodynamics analysis. In addition, the Rac1 activity in the myocardium and the expression levels of Rac1, p47phox and p67phox were measured by RT-PCR and western blot.

Results: Rats in ISO group developed into heart failure with decreased cardiac function. The Rac1, p47phox and p67phox mRNA expressions and ROS release were increased in ISO group. Atorvastatin treatment improved cardiac function of rats with isoproterenol-induced chronic heart failure and decreased the Rac1, p47phox and p67phox mRNA expressions. Also, membrane protein expression of Rac1 and ROS release decreased significantly.

Conclusions: Atorvastatin may improve cardiac function of rats with heart failure via inhibiting Rac1/P47phox/P67phox-mediated ROS release.

MeSH terms

  • Animals
  • Atorvastatin / pharmacology
  • Atorvastatin / therapeutic use*
  • Chronic Disease
  • Heart Failure / drug therapy
  • Heart Failure / metabolism*
  • Heart Failure / physiopathology
  • Hemodynamics / drug effects
  • Hemodynamics / physiology
  • Humans
  • Male
  • NADH, NADPH Oxidoreductases / antagonists & inhibitors
  • NADH, NADPH Oxidoreductases / metabolism*
  • NADPH Oxidases / antagonists & inhibitors
  • NADPH Oxidases / metabolism*
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism*
  • rac1 GTP-Binding Protein / antagonists & inhibitors
  • rac1 GTP-Binding Protein / metabolism*

Substances

  • Reactive Oxygen Species
  • Atorvastatin
  • NADH, NADPH Oxidoreductases
  • NCF2 protein, rat
  • NADPH Oxidases
  • neutrophil cytosolic factor 1
  • Rac1 protein, rat
  • rac1 GTP-Binding Protein