Improvement of Angiogenic Biomarkers Following Aerobic Training in Rats With Experimental Myocardial Infarction

Document Type : Original Article


1 Department of Physical Education and Sports Sciences, Mahallat Branch, Islamic Azad University, Mahallat, IR Iran.

2 Department of Physical Education, Pardis Branch, Islamic Azad University, Pardis, IR Iran.


Background: The present study aimed to compare 4 weeks of exercise (EXE) on the plasma levels of angiogenic markers in male and female rats with experimental myocardial infarction (MI).
Methods: Forty male and female Wistar rats were randomly and equally divided into 4 groups: male MI, male MI + EXE, female MI, and female MI + EXE. Subcutaneous injection of isoproterenol (150 mg/kg) was used to induce MI. The training groups performed an endurance training protocol on the treadmill for 4 weeks (speed=18 m/min, 30 min, 5 sessions per week). Sacrifice and blood sampling were performed 24 hours after the last training session. The data were analyzed using 2-way ANOVA and LSD post hoc tests.
Results: Vascular endothelial growth factor levels were significantly higher in the female MI + EXE group than in the male MI + EXE group (P=0.037). Changes in matrix metalloproteinase 2 levels were greater in the female rat group than in the male rat group (P=0.017). Matrix metalloproteinase 9 levels were higher in the MI + EXE female rats than in the MI + EXE male rats (P=0.008).
Conclusions: Our findings showed that sports rehabilitation had positive effects on experimental MI, which is likely to cause clinical changes and improve angiogenic parameters in female rats more than in male rats. (Iranian Heart Journal 2022; 23(3): 24-32)


  1. Zhang R, Lan C, Pei H, Duan G, Huang L, Li L. Expression of circulating miR-486 and miR-150 in patients with acute myocardial infarction. BMC cardiovascular disorders. 2015;15(1):51.
  2. Chen W, Woods SL, Puntillo KA. Gender differences in symptoms associated with acute myocardial infarction: a review of the research. Heart & Lung. 2005;34(4):240-7.
  3. Maleki Poya M, Abedi B, Palizvan M, Saremi A. The Effect of Eight Weeks of Incremental Endurance Training on The Levels of Matrix Metalloproteinase-1 (MMP1) and Thrombosponidine-1 (TSP1) in the Rats, Induced by Myocardial Infarction by Isoproterenol. Arak University of Medical Sciences. 2019;22(3):118-28.
  4. Freedman SB, Isner JM. Therapeutic angiogenesis for ischemic cardiovascular disease. Journal of molecular and cellular cardiology. 2001;33(3):379-93.
  5. Niu J, Han X, Qi H, Yin J, Zhang Z, Zhang Z. Correlation between vascular endothelial growth factor and long‑term prognosis in patients with acute myocardial infarction. Experimental and therapeutic medicine. 2016;12(1):475-9.
  6. Hoke M, Winter M-P, Wagner O, Exner M, Schillinger M, Arnold Z, et al. The impact of selectins on mortality in stable carotid atherosclerosis. Thrombosis and haemostasis. 2015;114(09):632-8.
  7. Ma Y, de Castro Brás LE, Toba H, Iyer RP, Hall ME, Winniford MD, et al. Myofibroblasts and the extracellular matrix network in post-myocardial infarction cardiac remodeling. Pflügers Archiv-European Journal of Physiology. 2014; 466(6):1113-27.
  8. Murillo CA, Woodside KJ, Guo Q, Zhang S, O'Connor KL, Hunter GC. Integrin and matrix metalloproteinase expression in human carotid plaque. Journal of Surgical Research. 2009; 155(1):157-64.
  9. Liu P, Sun M, Sader S. Matrix metalloproteinases in cardiovascular disease. Canadian Journal of Cardiology. 2006; 22:25B-30B.
  10. Christia P, Frangogiannis NG. Targeting inflammatory pathways in myocardial infarction. European journal of clinical investigation. 2013;43(9):986-95.
  11. Maleki MJ, Fatolahi H, Feylizadeh A, Abedi B. The effect of rehabilitation training and total checkup as a noninvasive method on hemodynamic parameters in patients who candidate for heart transplantation. International Archives of Health Sciences. 2019;6(1):24-9.
  12. Rahmati-Ahmadabad S, Azarbayjani M-A, Farzanegi P, Moradi L. High-intensity interval training has a greater effect on reverse cholesterol transport elements compared with moderate-intensity continuous training in obese male rats. European Journal of Preventive Cardiology. 2019:2047487319887828.
  13. Haas TL, Nwadozi E. Regulation of skeletal muscle capillary growth in exercise and disease. Applied Physiology, Nutrition, and Metabolism. 2015;40(12):1221-32.
  14. Pedersen BK. Anti‐inflammatory effects of exercise: role in diabetes and cardiovascular disease. European journal of clinical investigation. 2017;47(8):600-11.
  15. Elshazly A, Khorshid H, Hanna H, Ali A. Effect of exercise training on heart rate recovery in patients post anterior myocardial infarction. The Egyptian Heart Journal. 2018;70(4):283-5.
  16. Brown DA, Lynch JM, Armstrong CJ, Caruso NM, Ehlers LB, Johnson MS, et al. Susceptibility of the heart to ischaemia–reperfusion injury and exercise‐induced cardioprotection are sex‐dependent in the rat. The Journal of physiology. 2005;564(2):619-30.
  17. Lloyd PG, Prior BM, Yang HT, Terjung RL. Angiogenic growth factor expression in rat skeletal muscle in response to exercise training. American Journal of Physiology-Heart and Circulatory Physiology. 2003; 284(5):H1668-H78.
  18. Bertinchant JP, Robert E, Polge A, Marty-Double C, Fabbro-Peray P, Poirey S, et al. Comparison of the diagnostic value of cardiac troponin I and T determinations for detecting early myocardial damage and the relationship with histological findings after isoprenaline-induced cardiac injury in rats. Clinica Chimica Acta. 2000;298(1):13-28.
  19. Sun Y, Qi G, Li D, Meng H, Zhu Z, Zhao Y, et al. Walnut (Juglans regia L.) Kernel Extracts Protect Against Isoproterenol-Induced Myocardial Infarction in Rats. Rejuvenation research. 2019;22(4):306-12.
  20. Alimohammadi R, Naderi S, Allahtavakoli M. Effects of Exercise and Estrogen on Anxiety-like Behaviors in‎ Ovariectomized Mice. Journal of Babol University of Medical Sciences. 2015;17(12):40-6.
  21. Karbalaeifar S, Gaeini AA, Kordi MR, Nuri R, Ghorbani P. Effect of 6 Weeks High Intensity Interval Training on Selected Factors of Cardiac Angiogenesis in Rats with Myocardial Infarction. Sport Physiology. 2019; 11(42):17-30.
  22. Tolouei Azar J, Ravasi A, soori R, Akbarnejat A, Hemati Nafar M. The Comparison of the Effect of 8 Weeks of Aerobic and Resistance Training on Angiogenic (VEGF) and Angiostatic (ES) Factors in Sedentary Women. Journal of Sport Biosciences. 2019;11(1):1-16.
  23. Azamian Jazi A, Haffezi MR, Opera H, Abdi H. The effect of endurance exercise training and atorvastatin on VEGF in rat following experimental myocardial infarction. scientific journal of ilam university of medical sciences. 2016; 24(4):21-31.
  24. Wu G, Rana JS, Wykrzykowska J, Du Z, Ke Q, Kang P, et al. Exercise-induced expression of VEGF and salvation of myocardium in the early stage of myocardial infarction. American Journal of Physiology-Heart and Circulatory Physiology. 2009; 296(2):H389-H95.
  25. Rodríguez I, González M. Physiological mechanisms of vascular response induced by shear stress and effect of exercise in systemic and placental circulation. Frontiers in pharmacology. 2014; 5:209.
  26. Wan W, Powers AS, Li J, Zhang JQ, Ji L, Erikson JM. Effect of Post–Myocardial Infarction Exercise Training on the Renin-Angiotensin-Aldosterone System and Cardiac Function. The American journal of the medical sciences. 2007;334(4):265-73.
  27. Malamitsi-Puchner A, Tziotis MD J, Tsonou MSc A, Protonotariou E, Sarandakou A, Creatsas G. Changes in Serum Levels of Vascular Endothelial Growth Factor in Males and Females Throughout Life. The Journal of the Society for Gynecologic Investigation. 2000;7(309-312).
  28. Ranjbar K, Nazem F, Gholami MR, Nezami AR, Ardakanizade M, Sohrabi M, et al. Synergistic effects of nitric oxide and exercise on revascularisation in the infarcted ventricle in a murine model of myocardial infarction. PMC. 2015;14(EXCLI J):1104-015.
  29. Bordbarazari B, Gholami M, Ebrahim K, Abed Natanzi H, Ghazalian F. The effect of endurance training along with L-arginine supplementation on the levels of MMP-2 and MMP-9 in postmenopausal hypertensive women. Journal of Basic Research in Medical Sciences. 2019;6(4):20-8.
  30. Gao M, Lu X, Chen W, Xiao GH, Zhang Y, Yu R, et al. Randomized clinical trial of physiological ischemic training for patients with coronary heart disease complicated with heart failure: Safety of training, VEGF of peripheral blood and quality of life. Experimental and therapeutic medicine. 2018;16(1):260-4.