Document Type : Research Paper I Open Access I Released under CC BY-NC 4.0 license


1 PhD Student of Exercise Physiology, Department of Physical Education, Tabriz Branch, Islamic Azad University, Tabriz, Iran

2 Assistant Professor, Department of Physical Education, Tabriz Branch, Islamic Azad University, Tabriz, Iran

3 Associate Professor of Exercise Physiology, Department of Physical Education, Tabriz Branch, Islamic Azad University, Tabriz, Iran

4 . Associate Professor, Department of Exercise Physiology, Azarbaijan Shahid Madani University, Tabriz, Iran

5 Associate Professor, Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Tabriz University, Tabriz, Iran


The effects of high intensity interval training (HIIT) and curcumin supplementation on CD31+ capillary cell count and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP9) in left ventricle (LV) of male rats in the model of myocardial infraction were determined in this study. 40 male rats were divided into four groups: HIIT, curcumin, concomitant (HIIT+CUR) and control following isoproterenol induced myocardial infarction. Curcumin was administered through oral gavage as 15 mg/kgbw/day. HIIT was performed for 8 weeks, 5 sessions a week and included 60 minutes of interval running (4 min. of running with the intensity of 85-90% of VO2max and 2 min. of active recovery with the intensity of 50-60%). The results showed that HIIT in both HIIT and concomitant groups significantly increased LV VEGF protein expression (P=0.001) while no effect was noted for curcumin (P>0.05). Only curcumin significantly reduced (P=0.001) LV MMP9 protein expression (in both curcumin and concomitant groups). All three interventions significantly increased LV CD31+ capillary cell count (P=0.001). A significantly greater effect was noted for HIIT than curcumin (P=0.001) and for concomitant than both HIIT and curcumin (P=0.001). The results showed that all three interventions including curcumin, HIIT and concomitant were involved in capillary proliferation following infraction; however, curcumin induced capillary growth seems to occur through paths independent of VEGF as well. But the exact function of MMP9 down-regulation induced by curcumin is still unclear and more research is required because of the study limitations.


Main Subjects

1.   Forte E, Panahi M, Ng FS, Boyle J, Branca J, Bedard O, et al. Myocardial damage induced by a single high dose of isoproterenol in C57Bl/6J mice triggers a persistent adaptive immune response against the heart. BioRxiv. 2020.
2.   Ríos-Navarro C, Hueso L, Díaz A, Marcos-Garcés V, Bonanad C, Ruiz-Sauri A, et al. Role of antiangiogenic VEGF-A165b in angiogenesis and systolic function after reperfused myocardial infarction. Revista Española de Cardiología (English Edition). 2020.
3.   Wo D, Chen J, Li Q, Ma E, Yan H, Peng J, et al. IGFBP‐4 enhances VEGF‐induced angiogenesis in a mouse model of myocardial infarction. Journal of cellular and molecular medicine. 2020;24(16):9466-71.
4.   Anversa P, Beghi C, Kikkawa Y, Olivetti G. Myocardial infarction in rats. Infarct size, myocyte hypertrophy, and capillary growth. Circulation Research. 1986;58(1):26-37.
5.   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.
6.   Garza MA, Wason EA, Zhang JQ. Cardiac remodeling and physical training post myocardial infarction. World journal of cardiology. 2015;7(2):52.
7.   Leosco D, Rengo G, Iaccarino G, Golino L, Marchese M, Fortunato F, et al. Exercise promotes angiogenesis and improves beta-adrenergic receptor signalling in the post-ischaemic failing rat heart. Cardiovasc Res. 2008;78(2):385-94.
8.   Shiojima I. Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure. Journal of Clinical Investigation. 2005;115(8):2108-18.
9.   Wang B, Zhou R, Wang Y, Liu X, Shou X, Yang Y, et al. Effect of high-intensity interval training on cardiac structure and function in rats with acute myocardial infarct. Biomedicine & Pharmacotherapy. 2020;131:110690.
10. Ghosh SS, Salloum FN, Abbate A, Krieg R, Sica DA, Gehr TW, et al. Curcumin prevents cardiac remodeling secondary to chronic renal failure through deactivation of hypertrophic signaling in rats. American Journal of Physiology-Heart and Circulatory Physiology. 2010;299(4):H975-H84.
11. Moieni A, Hosseini SA. Effect of Resistance Training Combined with Curcumin Supplementation on Expression of Regulatory Genes Related to Myocardial Remodeling in Obese Rats. Journal of Applied Health Studies in Sport Physiology. 2020;7(2):45-52.
12. Majidi A, Poozesh Jadidi R, Azali Alamdari K, Bashiri J, Nourazar MAR. Effects of Aerobic Training and Curcumin Supplementation on Cardiomyocyte Apoptosis and MiRNAs Expression in Rats Exposed to Arsenic. Sport Physiology. 2020;12(48):39-60.
13. Wang NP, Wang ZF, Tootle S, Philip T, Zhao ZQ. Curcumin promotes cardiac repair and ameliorates cardiac dysfunction following myocardial infarction. Br J Pharmacol. 2012;167(7):1550-62.
14. Wang N-P, Wang Z-F, Tootle S, Philip T, Zhao Z-Q. Curcumin promotes cardiac repair and ameliorates cardiac dysfunction following myocardial infarction. British Journal of Pharmacology. 2012;167(7):1550-62.
15. Ma J, Ma SY, Ding CH. Curcumin reduces cardiac fibrosis by inhibiting myofibroblast differentiation and decreasing transforming growth factor beta1 and matrix metalloproteinase 9 / tissue inhibitor of metalloproteinase 1. Chinese journal of integrative medicine. 2017;23(5):362-9.
16. Vanhoutte D, Schellings M, Pinto Y, Heymans S. Relevance of matrix metalloproteinases and their inhibitors after myocardial infarction: A temporal and spatial window. Cardiovascular Research. 2006;69(3):604-13.
17. HOU Y, BO H, LIU Z. Effects of exercises training on myocardial remodeling and MMP-2 and MMP-9 expressions in post myocardial infarction rats. Chinese Journal of Rehabilitation Medicine. 2010(3):4.
18. Bellafiore M, Battaglia G, Bianco A, Farina F, Palma A, Paoli A. The involvement of MMP-2 and MMP-9 in heart exercise-related angiogenesis. Journal of translational medicine. 2013;11(1):283.
19. Xu D-P, Zou D-Z, Qiu H-L, Wu H-L. Traditional Chinese medicine ShenZhuGuanXin granules mitigate cardiac dysfunction and promote myocardium angiogenesis in myocardial infarction rats by upregulating PECAM-1/CD31 and VEGF expression. Evidence-Based Complementary and Alternative Medicine. 2017;2017.
20. Islam D, Banerjee Shanta M, Akhter S, Lyzu C, Hakim M, Islam MR, et al. Cardioprotective effect of garlic extract in isoproterenol-induced myocardial infarction in a rat model: assessment of pro-apoptotic caspase-3 gene expression. Clinical Phytoscience. 2020;6(1):67.
21. Kraljevic J, Marinovic J, Pravdic D, Zubin P, Dujic Z, Wisloff U, et al. Aerobic interval training attenuates remodelling and mitochondrial dysfunction in the post-infarction failing rat heart. Cardiovascular research. 2013;99(1):55-64.
22. Høydal MA, Wisløff U, Kemi OJ, Ellingsen Ø. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. European Journal of Preventive Cardiology. 2007;14(6):753-60.
23. Biswas J, Roy S, Mukherjee S, Sinha D, Roy MJAPjocpA. Indian spice curcumin may be an effective strategy to combat the genotoxicity of arsenic in Swiss albino mice. 2010;11(1):239.
24. Grimm D, Elsner D, Schunkert H, Pfeifer M, Griese D, Bruckschlegel G, et al. Development of heart failure following isoproterenol administration in the rat: role of the renin-angiotensin system. Cardiovascular research. 1998;37(1):91.
25. Sushamakumari S, Jayadeep A, Kumar J, Menon V. Effect of carnitine on malondialdehyde, taurine and glutathione levels in heart of rats subjected to myocardial stress by isoproterenol. Indian Journal of Experimental Biology. 1989;27(2):134.
26. Nirmala C, Puvanakrishnan R. Protective role of curcumin against isoproterenol induced myocardial infarction in rats. Molecular and cellular biochemistry. 1996;159(2):85-93.
27. Wu G, Luo J, Rana JS, Laham R, Sellke FW, Li J. Involvement of COX-2 in VEGF-induced angiogenesis via P38 and JNK pathways in vascular endothelial cells. Cardiovascular research. 2006;69(2):512-9.
28. 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.
29. Izanlu F, Rezaeian N, Pekand M. Effect of High Intensity Interval Training Versus Aerobic Training on Serum Levels of Angiopoietin-Like 4 and Lipids Profile in Elite Handball player Girls. Journal of Applied Health Studies in Sport Physiology. 2020;7(1):9-18.
30. Ebadi B, Damirchi A, Alamdari KA, Darbandi-Azar A, Naderi N. Cardiomyocyte mitochondrial dynamics in health and disease and the role of exercise training: A brief review. Research in Cardiovascular Medicine. 2018;7(3):107-15.
31. Diniz C, Suliburska J, Ferreira IM. New insights into the antiangiogenic and proangiogenic properties of dietary polyphenols. Molecular nutrition & food research. 2017;61(6):1600912.
32. Park JJ, Hwang SJ, Park J-H, Lee H-J. Chlorogenic acid inhibits hypoxia-induced angiogenesis via down-regulation of the HIF-1α/AKT pathway. Cellular Oncology. 2015;38(2):111-8.
33. Muresan A, Suciu S, Daicoviciu D, Filip A, Clichici S. Grape seed extract effects in brain after hypobaric hypoxia. Journal of medicinal food. 2013;16(9):831.
34. Iyer RP, Jung M, Lindsey ML. MMP-9 signaling in the left ventricle following myocardial infarction. American Journal of Physiology-Heart and Circulatory Physiology. 2016;311(1):H190-H8.
35. Bendeck MP. Macrophage matrix metalloproteinase-9 regulates angiogenesis in ischemic muscle. Circulation research. 2004;94(2):138-9.
36. Phatharajaree W, Phrommintikul A, Chattipakorn N. Matrix metalloproteinases and myocardial infarction. Canadian Journal of Cardiology. 2007;23(9):727-33.
37. Boarescu P-M, Chirilă I, Bulboacă AE, Bocșan IC, Pop RM, Gheban D, et al. Effects of curcumin nanoparticles in isoproterenol-induced myocardial infarction. Oxidative medicine and cellular longevity. 2019;2019.
38. Xiao J, Sheng X, Zhang X, Guo M, Ji X. Curcumin protects against myocardial infarction-induced cardiac fibrosis via SIRT1 activation in vivo and in vitro. Drug design, development and therapy. 2016;10:1267.
39. Liao Z, Li D, Chen Y, Li Y, Huang R, Zhu K, et al. Early moderate exercise benefits myocardial infarction healing via improvement of inflammation and ventricular remodelling in rats. Journal of Cellular and Molecular Medicine. 2019;23(12):8328-42.
40. Verma A, Meris A, Skali H, Ghali JK, Arnold JMO, Bourgoun M, et al. Prognostic Implications of Left Ventricular Mass and Geometry Following Myocardial Infarction. JACC: Cardiovascular Imaging. 2008;1(5):582.