Effects of HIIT and Curcumin Supplementation on MiR-208, MiR-499 and HSP60 Expression Level in Rat Model of Isoproterenol Induced Myocardial Infraction

Document Type : Research Paper

Authors

1 1. Ph.D student of Exercise Physiology, Department of Sport Physiology, Faculty of Educational Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil, Iran

2 Associate Professor of Exercise Physiology, Faculty of Educational Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil, Iran

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

4 Assistant Professor of Exercise Physiology, Faculty of Educational Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil, Iran

Abstract

The purpose of this study was to investigate effects of high intensity interval training (HIIT) and curcumin supplementation on cardiomyocyte miR-208, miR-499 and HSP60 expression level in rat model of isoproterenol induced acute myocardial infraction (AMI). 40 male rats (200-250 gr, age: 16 weeks old) were randomized into four groups of Training, Curcumin, Concomitant (HIIT+ Curcumin) and Control following intraperitoneal injection of isoproterenol (100 mg/kg) for two consecutive days to induce myocardial infarction. HIIT were done for eight weeks, 5 sessions a week for 60 min. Each session was included to 10 intervals (each interval for 4 min) of running at 85-90% of v VO2 peak with 2 min of active recovery at 50 to 60% of v VO2 peak. Curcumin was administrated through oral gavage 15 mg/kg a day. Expression levels of miR-208, miR-499 and HSP60 genes was evaluated using Real-Time PCR method. All three interventions of training, curcumin and their combination (HIIT+Curcumin) significantly elevated cardiac miR-499, HSP60 expression level as well as Vo2max improvement; meanwhile, miR-208 expression was reduced (p=0.001 under any circumstances). Moreover, the expression levels of miR-208 in the concomitant group were significantly lower than HHI (p=0.03) or curcumin (p=0.049) either. All three interventions are likely associated with alleviation of MI complications e.g. oxidative stress, ischemia/reperfusion injury and tissue remodeling, through modifications in microRNAs expression level. Moreover, a further reduction in miR-208 expression level in the concomitant group could imply on a lesser mortality rate or recurrent AMIs as well as a better cardiac structural remodeling following to infraction; emphasizing on better results with curcumin plus HIIT co-prescription. However, more investigations are warranted because of no straight measurement of many factors and also limitations in this study. 

Keywords

References

  1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. circulation. 2016;133(4):e38-e360.
  2. Weintraub WS, Daniels SR, Burke LE, Franklin BA, Goff Jr DC, Hayman LL, et al. Value of primordial and primary prevention for cardiovascular disease: a policy statement from the American Heart Association. Circulation. 2011;124(8):967-90.
  3. Sun T, Dong Y-H, Du W, Shi C-Y, Wang K, Tariq M-A, et al. The role of microRNAs in myocardial infarction: from molecular mechanism to clinical application. International journal of molecular sciences. 2017;18(4):745.
  4. Guidelines ECfP, Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, et al. Third universal definition of myocardial infarction. Journal of the American College of Cardiology. 2012;60(16):1581-98.
  5. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD. Third universal definition of myocardial infarction. Circulation. 2012;126(16):2020-35.
  6. Libby P. Mechanisms of acute coronary syndromes and their implications for therapy. N Engl J Med. 2013;368:2004-13.
  7. Wang X, Guo Z, Ding Z, Mehta JL. Inflammation, autophagy, and apoptosis after myocardial infarction. Journal of the American Heart Association. 2018;7(9):e008024.
  8. Haunsberger SJ, Connolly NM, Prehn JH. miRNAmeConverter: an R/bioconductor package for translating mature miRNA names to different miRBase versions. Bioinformatics. 2017;33(4):592-3.
  9. Li P, Li S-Y, Liu M, Ruan J-W, Wang Z-D, Xie W-C. Value of the expression of miR-208, miR-494, miR-499 and miR-1303 in early diagnosis of acute myocardial infarction. Life sciences. 2019;232:116547.
  10. Meng L-D, Meng A-C, Zhu Q, Jia R-Y, Kong Q-Z. Effect of microRNA-208a on mitochondrial apoptosis of cardiomyocytes of neonatal rats. Asian Pacific journal of tropical medicine. 2015;8(9):747-51.
  11. Yin K, Liu M, Zhang M, Wang F, Fen M, Liu Z, et al. miR-208a-3p suppresses cell apoptosis by targeting PDCD4 in gastric cancer. Oncotarget. 2016;7(41):67321.
  12. Tony H, Meng K, Wu B, Yu A, Zeng Q, Yu K, et al. MicroRNA-208a dysregulates apoptosis genes expression and promotes cardiomyocyte apoptosis during ischemia and its silencing improves cardiac function after myocardial infarction. Mediators of Inflammation. 2015: 479123.
  13. Bian C, Xu T, Zhu H, Pan D, Liu Y, Luo Y, et al. Luteolin inhibits ischemia/reperfusion-induced myocardial injury in rats via downregulation of microRNA-208b-3p. PLoS One. 2015;10(12):e0144877.
  14. Liu X, Meng H, Jiang C, Yang S, Cui F, Yang P. Differential microRNA expression and regulation in the rat model of post-infarction heart failure. PLoS One. 2016;11(8):e0160920.
  15. Wang X, Yang C, Liu X, Yang P. Ghrelin alleviates angiotensin II-induced H9c2 apoptosis: impact of the miR-208 family. Medical science monitor: international medical journal of experimental and clinical research. 2018;24:6707.
  16. Xiao Y, Zhao J, Tuazon JP, Borlongan CV, Yu G. MicroRNA-133a and Myocardial Infarction. Cell transplantation. 2019:0963689719843806.
  17. Wang J-X, Jiao J-Q, Li Q, Long B, Wang K, Liu J-P, et al. miR-499 regulates mitochondrial dynamics by targeting calcineurin and dynamin-related protein-1. Nature medicine. 2011;17(1):71-8.
  18. Chistiakov DA, Orekhov AN, Bobryshev YV. Cardiac-specific miRNA in cardiogenesis, heart function, and cardiac pathology (with focus on myocardial infarction). Journal of molecular and cellular cardiology. 2016;94:107-21.
  19. Li L, Li S, Wu M, Chi C, Hu D, Cui Y, et al. Early diagnostic value of circulating microRNAs in patients with suspected acute myocardial infarction. Journal of cellular physiology. 2019;234(8):13649-58.
  20. Abdou DM, Aziz EE, Kazem YS, Elgabrty S, Taha HS. The diagnostic value of circulating microRNA-499 versus high-sensitivity cardiac troponin T in early diagnosis of ST segment elevation myocardial infarction. Comparative Clinical Pathology. 2021: 30:565–570.
  21. Lize M, Pilarski S, Dobbelstein M. E2F1-inducible microRNA 449a/b suppresses cell proliferation and promotes apoptosis. Cell Death & Differentiation. 2010;17(3):452-8.
  22. Wang J, Jia Z, Zhang C, Sun M, Wang W, Chen P, et al. miR-499 protects cardiomyocytes from H2O2-induced apoptosis via its effects on Pdcd4 and Pacs2. RNA biology. 2014;11(4):339-50.
  23. Callis TE, Pandya K, Seok HY, Tang R-H, Tatsuguchi M, Huang Z-P, et al. MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. The Journal of clinical investigation. 2009;119(9):2772-86.
  24. Lin L, Kim S-C, Wang Y, Gupta S, Davis B, Simon SI, et al. HSP60 in heart failure: abnormal distribution and role in cardiac myocyte apoptosis. American Journal of Physiology-Heart and Circulatory Physiology. 2007;293(4):H2238-H47.
  25. Novo G, Cappello F, Rizzo M, Fazio G, Zambuto S, Tortorici E, et al. Hsp60 and heme oxygenase-1 (Hsp32) in acute myocardial infarction. Translational research. 2011;157(5):285-92.
  26. Krishnan‐Sivadoss I, Mijares‐Rojas IA, Villarreal‐Leal RA, Torre‐Amione G, Knowlton AA, Guerrero‐Beltrán CE. Heat shock protein 60 and cardiovascular diseases: An intricate love‐hate story. Medicinal Research Reviews. 2021;41(1):29-71.
  27. Duan Y, Tang H, Mitchell-Silbaugh K, Fang X, Han Z, Ouyang K. Heat shock protein 60 in cardiovascular physiology and diseases. Frontiers in Molecular Biosciences. 2020; 30;7:73.
  28. Wang NP, Wang ZF, Tootle S, Philip T, Zhao ZQ. Curcumin promotes cardiac repair and ameliorates cardiac dysfunction following myocardial infarction. British journal of pharmacology. 2012;167(7):1550-62.
  29. 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; 1;24(15):2802.
  30. Lv FH, Yin HL, He YQ, Wu HM, Kong J, Chai XY, et al. Effects of curcumin on the apoptosis of cardiomyocytes and the expression of NF-κB, PPAR-γ and Bcl-2 in rats with myocardial infarction injury. Experimental and therapeutic medicine. 2016;12(6):3877-84.
  31. Yu L, Fan Y, Ye G, Li J, Feng X, Lin K, et al. Curcumin inhibits apoptosis and brain edema induced by hypoxia-hypercapnia brain damage in rat models. The American journal of the medical sciences. 2015;349(6):521-5.
  32. Tao P, Yin H, Ma Y. Study of the mechanisms of curcumin on mitochondrial permeability transition of hepatocytes in rats with sepsis. Zhonghua wei zhong bing ji jiu yi xue. 2014;26(9):666-70.
  33. Somasundaram S, Edmund NA, Moore DT, Small GW, Shi YY, Orlowski RZ. Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer research. 2002;62(13):3868-75.
  34. Bulku E, J Stohs S, Cicero L, Brooks T, Halley H, D Ray S. Curcumin exposure modulates multiple pro-apoptotic and anti-apoptotic signaling pathways to antagonize acetaminophen-induced toxicity. Current neurovascular research. 2012;9(1):58-71.
  35. Nirmala C, Puvanakrishnan R. Protective role of curcumin against isoproterenol induced myocardial infarction in rats. Molecular and cellular biochemistry. 1996;159(2):85-93.
  36. de Souza Vieira S, Antonio EL, de Melo BL, Portes LA, Montemor J, Oliveira HA, et al. Exercise training potentiates the cardioprotective effects of stem cells post-infarction. Heart, Lung and Circulation. 2019;28(2):263-71.
  37. Zhao D, Sun Y, Tan Y, Zhang Z, Hou Z, Gao C, et al. Short-Duration Swimming Exercise After Myocardial Infarction Attenuates Cardiac Dysfunction and Regulates Mitochondrial Quality Control in Aged Mice. Oxidative medicine and cellular longevity. 2018;2018:4079041.
  38. Schüttler D, Clauss S, Weckbach LT, Brunner S. Molecular mechanisms of cardiac remodeling and regeneration in physical exercise. Cells. 2019;8(10):1128.
  39. 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.
  40. 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.
  41. Zheng H, Xie N, Xu H, Huang J, Xie X, Luo M. Effects of 4 month exercise on left ventricular remodeling and autonomic nervous system in hypertensive patients. Panminerva medica. 2014;58(1):1-7.
  42. Abel ED, Doenst T. Mitochondrial adaptations to physiological vs. pathological cardiac hypertrophy. Cardiovascular research. 2011:cvr015.
  43. 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.
  44. Rodrigues B, Figueroa DM, Mostarda CT, Heeren MV, Irigoyen M-C, De Angelis KJCd. Maximal exercise test is a useful method for physical capacity and oxygen consumption determination in streptozotocin-diabetic rats. Cardiovasc Diabetol. 2007;6(1):38.
  45. 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.
  46. Waring CD, Vicinanza C, Papalamprou A, Smith AJ, Purushothaman S, Goldspink DF, et al. The adult heart responds to increased workload with physiologic hypertrophy, cardiac stem cell activation, and new myocyte formation. European heart journal. 2012;35(39):2722-31.
  47. Biswas J, Roy S, Mukherjee S, Sinha D, Roy M. Indian spice curcumin may be an effective strategy to combat the genotoxicity of arsenic in Swiss albino mice. Asian Pac J Cancer Prev. 2010;11(1):239-47.
  48. Soci UPR, Fernandes T, Barauna VG, Hashimoto NY, de Fátima Alves Mota G, Rosa KT, et al. Epigenetic control of exercise training-induced cardiac hypertrophy by miR-208. Clinical Science. 2016;130(22):2005-15.
  49. Wu X-D, Zeng K, Liu W-L, Gao Y-G, Gong C-S, Zhang C-X, et al. Effect of aerobic exercise on miRNA-TLR4 signaling in atherosclerosis. International Journal of Sports Medicine. 2014;35(04):344-50.
  50. 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.
  51. 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.
  52. Wang G-K, Zhu J-Q, Zhang J-T, Li Q, Li Y, He J, et al. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. European heart journal. 2010;31(6):659-66.
  53. Pinchi E, Frati P, Aromatario M, Cipolloni L, Fabbri M, La Russa R, et al. miR‐1, miR‐499 and miR‐208 are sensitive markers to diagnose sudden death due to early acute myocardial infarction. Journal of cellular and molecular medicine. 2019;23(9):6005-16.
  54. Corsten MF, Dennert R, Jochems S, Kuznetsova T, Devaux Y, Hofstra L, et al. Circulating MicroRNA-208b and MicroRNA-499 reflect myocardial damage in cardiovascular disease. Circulation: Cardiovascular Genetics. 2010;3(6):499-506.
  55. Alavi-Moghaddam M, Chehrazi M, Alipoor SD, Mohammadi M, Baratloo A, Mahjoub MP, et al. A preliminary study of microRNA-208b after acute myocardial infarction: impact on 6-month survival. Disease markers. 2018:2410451.
  56. Gidlöf O, Smith JG, Miyazu K, Gilje P, Spencer A, Blomquist S, et al. Circulating cardio-enriched microRNAs are associated with long-term prognosis following myocardial infarction. BMC cardiovascular disorders. 2013;13(1):1-9.
  57. Gidlöf O, Andersson P, Van Der Pals J, Götberg M, Erlinge D. Cardiospecific microRNA plasma levels correlate with troponin and cardiac function in patients with ST elevation myocardial infarction, are selectively dependent on renal elimination, and can be detected in urine samples. Cardiology. 2011;118(4):217-26.
  58. Wang X, Chen X, Xu H, Zhou S, Zheng Y, Keller BB, et al. Emerging roles of microRNA‐208a in cardiology and reverse cardio‐oncology. Medicinal Research Reviews. 2021; 41(4):2172-2194.
  59. Zhao X, Wang Y, Sun X. The functions of microRNA-208 in the heart. Diabetes research and clinical practice. 2020;160:108004.
  60. Canan BD, Haizlip KM, Xu Y, Monasky MM, Hiranandani N, Milani-Nejad N, et al. Effect of exercise training and myocardial infarction on force development and contractile kinetics in isolated canine myocardium. Journal of Applied Physiology. 2016;120(8):817-24.
  61. Bagheri A, Shakeri N, Nik Bakht H. The Effect of Physical Activity on cTNI, Visceral Fat, and Plasma Biomarkers of Cardiovascular Risk in Shift Workers of Sarir Plast Industrial Group. Jundishapur Journal of Chronic Disease Care. 2020; 9(1):e98150.( in Persian).
  62. Pinchi E, Frati P. miR-1, miR-499 and miR-208 are sensitive markers to diagnose sudden death due to early acute myocardial infarction. J Cell Mol Med. 2019;23(9):6005-16.
  63. Liu X, Fan Z, Zhao T, Cao W, Zhang L, Li H, et al. Plasma miR-1, miR-208, miR-499 as potential predictive biomarkers for acute myocardial infarction: An independent study of Han population. Experimental gerontology. 2015;72:230-8.
  64. Li C, Pei F, Zhu X, Duan DD, Zeng C. Circulating microRNAs as novel and sensitive biomarkers of acute myocardial Infarction. Clinical biochemistry. 2012;45(10-11):727-32.
  65. Zhao C, Cheng G, He R, Hong Y, Wan Q, Wang Z, et al. Analysis and clinical significance of microRNA-499 expression levels in serum of patients with acute myocardial infarction. Genet Mol Res. 2015;14(2):4027-34.
  66. Li Y, Lu J, Bao X, Wang X, Wu J, Li X, et al. MiR-499-5p protects cardiomyocytes against ischaemic injury via anti-apoptosis by targeting PDCD4. Oncotarget. 2016;7(24):35607.
  67. Cheng C, Wang Q, You W, Chen M, Xia J. MiRNAs as biomarkers of myocardial infarction: a meta-analysis. PloS one. 2014;9(2):e88566.
  68. Dastani M, Bigdelu L, Hoseinzadeh M, Rahimi HR, Karimani A, Mohammadpour AH, et al. The effects of curcumin on the prevention of atrial and ventricular arrhythmias and heart failure in patients with unstable angina: A randomized clinical trial. Avicenna journal of phytomedicine. 2019;9(1):1.
  69. jokar m, motamedi p. Evaluation of HSP60 and HSP70 Gene Expression Following High-Intensity Anaerobic Training after Ischemia-Reperfusion in Male Rats: Effect of Melatonin. Jundishapur Scientific Medical Journal. 2019;18(5):471-84. ( in Persian).
  70. Karataş R, Çelik M, Yılmaz A, Keles F, Aygül N, Vatansev H, et al. The value of heat shock protein (HSP) 60 on in-hospital and shortterm prognosis in patients with acute ST segment elevation myocardial infarction. J Surg Med. 2020;4:130-4.
  71. Wu J, Chen S, Liu Y, Liu Z, Wang D, Cheng Y. Therapeutic perspectives of heat shock proteins and their protein-protein interactions in myocardial infarction. Pharmacological Research. 2020;160:105162.
  72. Alizadeh Pahavani H, Rajabi H, Nabiuni M, Motamedi P, Khaledi N, Tayanloo A. The Effect of Aerobic Exercise with Medium and High Intensity on the Gene Expression of Bax (BCL2 Associated X) and Bcl-2 (B-Cell Lymphoma 2) Markers in Rat Myocard After Ischemic-Reperfusion. Sport Physiology. 2020;12(45):31-44. ( in Persian).
  73. Zhang H, K Tong T, Qiu W, Wang J, Nie J, He Y. Effect of high-intensity interval training protocol on abdominal fat reduction in overweight Chinese women: a randomized controlled trial. Kinesiology. 2015;47(1.):57-66.
Sport Physiology
Volume 13, Issue 52 - Serial Number 52
February 2022
Pages 85-110

Files

History

  • Receive Date: 07 June 2021
  • Revise Date: 28 September 2021
  • Accept Date: 29 September 2021

Share

How to cite

Statistics