Effect of rapamycin on the level of autophagy in rats with early heart failure

J Cell Biochem. 2019 Mar;120(3):4065-4070. doi: 10.1002/jcb.27691. Epub 2018 Oct 15.

Abstract

Objectives: Heart failure (HF) progression can be prevented by an inhibitor of the mammalian target of rapamycin and an autophagy enhancer rapamycin. This current study aimed to investigate the effect of rapamycin on HF progression and myocardial cells apoptosis.

Methods: HF rats were injected with low-, middle-, and high-dose rapamycin. Echocardiography, hematoxylin-eosin staining, plasma brain natriuretic peptide, myocardial cells apoptosis, and Akt activation in rapamycin-treated rats were detected.

Results: HF rats showed reduced cardiac functions, destructive pathological changes in the myocardium, enhanced Akt activation and myocardial cells apoptosis. However, rapamycin reversed all the changes in a dose-dependent manner. Cardiac functions were enhanced by rapamycin. Myocardial cells apoptotic percentage, Akt expression, and pathological changes of the myocardium in HF rats were inhibited by rapamycin administration.

Conclusions: Rapamycin protected against myocardial hypertrophy and myocardial cells apoptosis in HF rats in a dose-dependent manner.

Keywords: Akt; apoptosis; heart failure; rapamycin.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Autophagy / drug effects*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Echocardiography
  • Gene Expression Regulation / drug effects
  • Heart / drug effects*
  • Heart / physiopathology
  • Heart Failure / drug therapy*
  • Heart Failure / genetics
  • Heart Failure / pathology
  • Humans
  • Myocardium / metabolism
  • Natriuretic Peptide, Brain / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Rats
  • Signal Transduction / drug effects
  • Sirolimus / pharmacology*

Substances

  • Natriuretic Peptide, Brain
  • Proto-Oncogene Proteins c-akt
  • Sirolimus