Low doses of simvastatin therapy ameliorate cardiac inflammatory remodeling in Trypanosoma cruzi-infected dogs

Am J Trop Med Hyg. 2011 Feb;84(2):325-31. doi: 10.4269/ajtmh.2011.10-0451.

Abstract

Chagas cardiomyopathy remodeling is based on the presence of Trypanosoma cruzi in heart tissue and on the complex inflammatory response leading to a myocardium fibrosis and alterations in conductive and functional heart parameters. This study aims to evaluate Simvastatin on the inflammatory response and heart functionality using dogs infected with Y strain of T. cruzi. Animals were treated daily with Simvastatin (20 mg) for 6 months and submitted to clinical and immunopathological evaluations. Simvastatin reduced heart expression and serum levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) but not interleukin-10 (IL-10), possibly favoring blood parasitism but reducing inflammation and fibrosis in the left ventricle and right atrium. Simvastatin also ameliorated ejection fraction, diastolic diameter, and mass index of the left ventricle 6 months after infection. This study suggests that more investigation should be performed on the use of statins as a prophylactic therapy against cardiac remodeling because of their effects on modifying immune response and benefiting functional parameters in dogs with T. cruzi-induced ventricular dysfunctions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chagas Cardiomyopathy / drug therapy
  • Chagas Cardiomyopathy / veterinary*
  • Dog Diseases / drug therapy*
  • Dog Diseases / parasitology
  • Dogs
  • Female
  • Heart / drug effects
  • Heart / parasitology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Male
  • Myocardium / metabolism
  • Polymerase Chain Reaction / veterinary
  • Simvastatin / administration & dosage
  • Simvastatin / therapeutic use*
  • Stroke Volume / drug effects
  • Trypanosoma cruzi
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma
  • Simvastatin