[Atorvastatin induced increase in homologous angiotensin I converting enzyme (ACE2) mRNA is associated to decreased fibrosis and decreased left ventricular hypertrophy in a rat model of diabetic cardiomyopathy]

Rev Peru Med Exp Salud Publica. 2011 Jun;28(2):264-72. doi: 10.1590/s1726-46342011000200013.
[Article in Spanish]

Abstract

Objectives: This study has investigated the effect of atorvastatin on the progression of cardiac remodelling and ACE- 2 expression in diabetic myocardium in rats.

Materials and methods: Diabetes was induced in Holtzman rats with an intraperitoneal injection of streptozotocin. The animals were divided into 3 groups: (1) normal control rats, (2) diabetic rats and (3) diabetic rats treated orally with atorvastatin (50 mg/kg/day). After eight weeks of treatment, the hearts were removed for morphometric studies, collagen content assay and genetic expressions of ACE and ACE2 mRNA.

Results: Myocardial hypertrophy index and collagen deposition were increased in diabetic rats, but not in the treated-diabetic rats, without producing changes in cholesterol levels. Myocardial ACE mRNA levels were increased while ACE2 mRNA levels were decreased in diabetic rats. Atorvastatin administration attenuated overexpression of ACE mRNA and overexpression of ACE-2 mRNA in diabetic rats.

Conclusions: Our results indicate that atorvastatin, independently of its cholesterol-lowering capacity, lowers the ACE/ACE2 ratio to normal values and attenuates the development of adverse remodeling in the diabetic heart.

MeSH terms

  • Animals
  • Atorvastatin
  • Diabetic Cardiomyopathies / genetics*
  • Diabetic Cardiomyopathies / prevention & control*
  • Disease Models, Animal
  • Fibrosis / genetics
  • Fibrosis / prevention & control
  • Heptanoic Acids / therapeutic use*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypertrophy, Left Ventricular / genetics*
  • Male
  • Peptidyl-Dipeptidase A / genetics*
  • Pyrroles / therapeutic use*
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / drug effects*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • RNA, Messenger
  • Atorvastatin
  • Peptidyl-Dipeptidase A