High-intensity interval training increase GATA4, CITED4 and c-Kit and decreases C/EBPβ in rats after myocardial infarction

Life Sci. 2019 Mar 15:221:319-326. doi: 10.1016/j.lfs.2019.02.045. Epub 2019 Feb 22.

Abstract

Aim: Myocardial infarction (MI), an important cause of morbidity and mortality, can be followed by left ventricular dysfunction and cardiomyocyte loss. Cardiac repair mechanisms may subsequently improve left ventricular function. Exercise training has been suggested to have cardioprotective effects against MI damage, but detailed knowledge is lacking on the effects of different types and intensities of exercise training on molecular targets of cardiomyocyte regeneration.

Main methods: MI was induced in male Wistar rats by ligating the left anterior descending coronary artery. After MI induction, the rats were randomly assigned to one of five groups: sham operated, and experimental MI followed by no exercise, or low, moderate or high intensity exercise Cardiac function and infarct size were assessed by echocardiography and Evans blue/TTC staining, respectively. The expression of mRNA markers and proteins associated with myocardial regeneration was measured with RT-PCR and western blotting.

Key findings: Exercise training at different intensities improved cardiac function and levels of stem cell and cardiomyocyte markers, and reduced infarct size. mRNA levels of GATA4, Nkx2.5 and c-Kit and protein expression of Nkx2.5 and c-Kit were significantly increased in all MI-exercise groups. The high-intensity exercise group had greater increases than the low and moderate intensity exercise groups. In the high-intensity exercise group, Sca-1 and CITED4 increased more than in the low-intensity exercise group. C/EBPβ mRNA and protein levels decreased after exercise training, with greater reductions in the high-intensity exercise group than the low- or moderate-intensity groups.

Significance: The findings suggest that by targeting cardiogenesis, high-intensity training can exert cardioprotective effects against cardiac dysfunction in an experimental model of MI.

Keywords: Cardiac stem cell markers; High-intensity interval training; Myocardial infarction.

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Protein-beta
  • Coronary Vessels
  • Disease Models, Animal
  • Echocardiography
  • GATA4 Transcription Factor / metabolism
  • High-Intensity Interval Training / methods
  • Homeobox Protein Nkx-2.5 / metabolism
  • Male
  • Myocardial Infarction / metabolism*
  • Myocardium
  • Myocytes, Cardiac
  • Physical Conditioning, Animal / methods*
  • Physical Conditioning, Animal / physiology*
  • Proto-Oncogene Proteins c-kit / metabolism
  • Rats
  • Rats, Wistar
  • Ventricular Function, Left

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • GATA4 Transcription Factor
  • Gata4 protein, rat
  • Homeobox Protein Nkx-2.5
  • Nkx2-5 protein, rat
  • Proto-Oncogene Proteins c-kit