The effect of 8 weeks of high-intensity interval training and moderate-intensity continuous training on cardiac angiogenesis factor in diabetic male rats

J Physiol Biochem. 2020 May;76(2):291-299. doi: 10.1007/s13105-020-00733-5. Epub 2020 Mar 10.


The balance of pro-angiogenic and anti-angiogenic factors has a significant role in the development of diabetic cardiomyopathy. The purpose of this study was to examine the effect of 8 weeks of high-intensity interval training (HIIT) and moderate intensity continuous training (MICT) on the myocardial angiogenic factors and histological changes in male diabetic rats. Thirty-two male Wistar rats were randomly assigned into four groups: healthy non-exercised control, diabetic (D), D + HIIT, and D+ MICT groups. Diabetes type 2 was induced by a high-fat diet for 2 weeks and a single injection of streptozotocin. Following confirmation of diabetes, animals were subjected to HIIT (90 to 95% of VO2max) or MICT (50-65% of VO2max) protocols 5 days a week for 8 weeks. Western blotting was used for detection of protein expressions of vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), matrix metalloproteinase-2 (MMP2), and tissue inhibitor of matrix metalloproteinase-2 (TIMP2) in the left ventricle. In addition, baseline and final blood glucose and body weight were measured. Histological changes were evaluated using H&E and Masson's trichrome staining. The results showed that exercise increased protein levels of pro-angiogenic factors while reduced anti-angiogenic factors protein levels in diabetic animals. These changes were followed by increased capillary density and reduced interstitial fibrosis in the left ventricle. Moreover, the MICT was superior to HIIT in enhancing angiogenic factors and attenuation of blood glucose and fibrosis in the diabetic rats. These findings confirm the effectiveness of exercise, particularly MICT, in the improvement of diabetic cardiomyopathy.

Keywords: Angiogenesis; Diabetic cardiomyopathy; Fibrosis; MMP2; TIMP2; VEGF.

MeSH terms

  • Angiogenic Proteins / metabolism
  • Animals
  • Blood Glucose
  • Coronary Vessels / metabolism*
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetic Cardiomyopathies / metabolism*
  • Fibrosis
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Neovascularization, Physiologic*
  • Physical Conditioning, Animal / methods*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Transforming Growth Factor beta / metabolism
  • Vascular Endothelial Growth Factor A / metabolism


  • Angiogenic Proteins
  • Blood Glucose
  • Timp2 protein, rat
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat