Exercise promotes heart regeneration in aged rats by increasing regenerative factors in myocardial tissue

Physiol Int. 2020 Mar;107(1):166-176. doi: 10.1556/2060.2020.00008.

Abstract

Exercise-induced stem cell activation is implicated in cardiovascular regeneration. However, ageing limits the capacity of cellular and molecular remodelling of the heart. It has been shown that exercise improves structure regeneration and function in the process of ageing. Aged male Wistar rats (n = 24) were divided into three groups: Control (CO), High-intensity interval training (HIIT) (80-100% of the maximum speed), and continuous endurance training (CET) (60-70% of the maximum speed) groups. Training groups were trained for 6 weeks. The expression of the Nkx2.5 gene was determined by real-time (RT-PCRs) analysis. Immunohistochemical staining was performed to assess the C-kit positive cardiac progenitor and Ki67 positive cells. The mRNA level of Nkx2.5 was significantly increased in the CET and HIIT groups (P < 0.05). Also, cardiac progenitor cells positive for C-kit were increased in both the CET and HIIT groups (P < 0.05). Exercise training improved the ejection fraction and fractional shortening in both training groups (P < 0.05). This study indicated that training initiates the activation of cardiac progenitor cells, leading to the generation of new myocardial cells (R = 0.737, P = 0.001). It seems that C-kit positive cells in training groups showed an increase in the expression of some transcription factors (Nkx2.5 gene), representing an increased regenerative capacity of cardiomyocytes during the training period. These findings suggest that the endogenous regenerative capacity of the adult heart, mediated by cardiac stem cells, would be increased in response to exercise.

Keywords: C-kit; Nkx2.5; ageing; cardiac stem cell; exercise.

MeSH terms

  • Aging / physiology*
  • Animals
  • Heart / physiology*
  • Homeobox Protein Nkx-2.5 / genetics*
  • Motor Activity / physiology*
  • Myocardium* / metabolism
  • Myocardium* / pathology
  • Myocytes, Cardiac / physiology*
  • Physical Conditioning, Animal / methods
  • Proto-Oncogene Proteins c-kit / genetics*
  • Rats
  • Rats, Wistar
  • Regeneration / physiology*
  • Stem Cells / physiology
  • Stroke Volume
  • Transcriptional Activation

Substances

  • Homeobox Protein Nkx-2.5
  • Nkx2-5 protein, rat
  • Proto-Oncogene Proteins c-kit