1. bookVolume 3 (2020): Issue 4 (December 2020)
Journal Details
First Published
30 May 2018
Publication timeframe
1 time per year
access type Open Access

The Role of Oxidative Stress and Antioxidants in Occurrence of Myocardial Infarction and Chronic Heart Failure

Published Online: 31 Dec 2020
Page range: 155 - 164
Journal Details
First Published
30 May 2018
Publication timeframe
1 time per year

Oxidative stress is one of the most important mechanisms of cardiovascular diseases, especially in heart failure. Mitochondrial dysfunction and inflammation play a major role in formation of free radicals and antioxidants. The association between oxidative stress, telomere biology and cell senescence plays the key role in cardiovascular pathology development. The paper considers role of pro-oxidant and antioxidant enzymes in heart pathology development. Specifically, the role of such antioxidant enzymes as glutathione peroxidase 3, catalase, and superoxide dismutase is described. The role of gamma-glutamyl transferase is emphasized as its activity increases significantly in cases of heart failure, coronary heart disease, stroke, arterial hypertensions, and arrhythmias. This article is a literature review of the effect of such antioxidants as alpha-tocopherol, ubiquinone, uric acid, and triiodothyronine on development of heart failure and myocardial infarction. A decrease in triiodothyronine concentration is a risk factor for coronary heart disease. High uric acid values in patients with myocardial infarction upon admission to the hospital are associated with a high risk of sudden death. The influence of such minerals such as zinc, copper, magnesium, selenium, potassium, sodium, calcium, and iron on heart failure development has been analyzed. The role of ceruloplasmin as an independent predictor of acute and chronic cardiac disorders cardiac events, mortality, and bad prognosis in patients with heart failure and myocardial infarction is examined. The authors demonstrate the influence of inflammation on heart failure development as well as association of inflammation with oxidative stress.


1. Sack MN, Fyhrquist FY, Saijonmaa OJ, Fuster V, Kovacic JC. Basic Biology of Oxidative Stress and the Cardiovascular System: Part 1 of a 3-Part Series. J Am Coll Cardiol. 2017;70(2):196–211. https://doi.org/10.1016/j.jacc.2017.05.034Search in Google Scholar

2. Stocker R, Keaney JF Jr. Role of oxidative modifications in atherosclerosis. Physiol Rev. 2004;84(4):1381–478. https://doi.org/10.1152/physrev.00047.2003Search in Google Scholar

3. Rahal A, Kumar A, Singh V, Yadav B, Tiwari R, Chakraborty S, et al. Oxidative stress, prooxidants, and antioxidants: the interplay. Biomed Res Int. 2014;2014:761264. https://doi.org/10.1155/2014/761264Search in Google Scholar

4. Hill MF, Singal PK. Antioxidant and oxidative stress changes during heart failure subsequent to myocardial infarction in rats. Am J Pathol. 1996;148(1):291–300.Search in Google Scholar

5. Zip es DP, Libby P, Bonow RO, Mann DL, Tomaselli GF, editors. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, Single Volume. 11th edition. Elsevier; 2019. p. 1–2040.Search in Google Scholar

6. Wende AR, Brahma MK, McGinnis GR, Young ME. Metabolic Origins of Heart Failure. JACC Basic Transl Sci. 2017;2(3):297–310. https://doi.org/10.1016/j.jacbts.2016.11.009Search in Google Scholar

7. Münzel T, Camici GG, Maack C, Bonetti NR, Fuster V, Kovacic JC. Impact of Oxidative Stress on the Heart and Vasculature: Part 2 of a 3-Part Series. J Am Coll Cardiol. 2017;70(2):212–29. https://doi.org/10.1016/j.jacc.2017.05.035Search in Google Scholar

8. Razvi S, Jabbar A, Pingitore A, Danzi S, Biondi B, Klein I, et al. Thyroid Hormones and Cardiovascular Function and Diseases. J Am Coll Cardiol. 2018;71(16):1781–96. https://doi.org/10.1016/j.jacc.2018.02.045Search in Google Scholar

9. Zhu Z, Wang K, Wang J, Chi R, Yang Z, Xu H, et al. GW29-e1773 Enhanced oxidative stress mediates pathological autophagy in cardiac myocytes in pressure overload induced heart failure in rats. J Am Coll Cardiol. 2018;72(16):C58. https://doi.org/10.1016/j.jacc.2018.08.212Search in Google Scholar

10. Molina AJ, Bharadwaj MS, Van Horn C, Nicklas BJ, Lyles MF, Eggebeen J, et al. Skeletal Muscle Mitochondrial Content, Oxidative Capacity, and Mfn2 Expression Are Reduced in Older Patients With Heart Failure and Preserved Ejection Fraction and Are Related to Exercise Intolerance. JACC Heart Fail. 2016;4(8):636–45. https://doi.org/10.1016/j.jchf.2016.03.011Search in Google Scholar

11. Pastori D, Pignatelli P, Farcomeni A, Menichelli D, Nocella C, Carnevale R, et al. Aging-Related Decline of Glutathione Peroxidase 3 and Risk of Cardiovascular Events in Patients With Atrial Fibrillation. J Am Heart Assoc. 2016;5(9):e003682. https://doi.org/10.1161/JAHA.116.003682Search in Google Scholar

12. Bloomfield GS, Alenezi F, Barasa FA, Lumsden R, Mayosi BM, Velazquez EJ. Human Immunodeficiency Virus and Heart Failure in Low- and Middle-Income Countries. JACC Heart Fail. 2015;3(8):579–90. https://doi.org/10.1016/j.jchf.2015.05.003Search in Google Scholar

13. Heinecke JW. Oxidized amino acids: culprits in human atherosclerosis and indicators of oxidative stress. Free Radic Biol Med. 2002;32(11):1090–101. https://doi.org/10.1016/s0891-5849(02)00792-xSearch in Google Scholar

14. Chukaeva II, Orlova NV, Evdokimov FA, Aleshkin VA, Soloshenkova OO, Novikova LI, et al. Inflammation role and anti-inflammatory strategies in acute cardiovascular pathology. Russian Journal of Cardiology. 2009;(5):30–4. Russian. https://doi.org/10.15829/1560-4071-2009-5-30-34Search in Google Scholar

15. Witte KK, Byrom R. Micronutrients for chronic heart failure: end of the road or path to enlightenment? JACC Heart Fail. 2014;2(3):318–20. https://doi.org/10.1016/j.jchf.2014.04.001Search in Google Scholar

16. Dominguez-Rodriguez A, Abreu-Gonzalez P, Reiter RJ. Clinical aspects of melatonin in the acute coronary syndrome. Curr Vasc Pharmacol. 2009;7(3):367–73. https://doi.org/10.2174/157016109788340749Search in Google Scholar

17. Niemann B, Rohrbach S, Miller MR, Newby DE, Fuster V, Kovacic JC. Oxidative Stress and Cardiovascular Risk: Obesity, Diabetes, Smoking, and Pollution: Part 3 of a 3-Part Series. J Am Coll Cardiol. 2017;70(2):230–51. https://doi.org/10.1016/j.jacc.2017.05.043Search in Google Scholar

18. Terekhina NA, Goryacheva OG, Petrovich YuA, Reuk SE, Zubarev MA. The investigation of a 1-antitripsin, orozomukoid and ceruloplasmin in peripheral blood and oral fluid. paradontitis is one of more risk factors of cardiovascular diseases. Patologicheskaya Fiziologiya i Eksperimental’naya Terapiya. 2012;56(2):18–21. Russian.Search in Google Scholar

19. Goryacheva OG, Koziolova NA. Heart failure in human immunodeficiency virus-infected patients. Russian Journal of Cardiology. 2020;25(1):3706. Russian. https://doi.org/10.15829/1560-4071-2020-1-3706Search in Google Scholar

20. Zhu ZW, Tang JJ, Chai XP, Fang ZF, Liu QM, Hu XQ, et al. Comparison of heart failure and COVID-19 in chest CT features and clinical characteristics. Zhonghua Xin Xue Guan Bing Za Zhi. 2020;48(6):467–71. Chinese. https://doi.org/10.3760/cma.j.cn112148-20200218-00093Search in Google Scholar

21. Cheng ML, Chen C M, Ho HY, Li JM, Chiu DT. Effect of acute myocardial infarction on erythrocytic glutathione peroxidase 1 activity and plasma vitamin E levels. Am J Cardiol. 2009;103(4):471–75. https://doi.org/10.1016/j.amjcard.2008.09.104Search in Google Scholar

22. Emdin M, Pompella A, Paolicchi A. Gamma-glutamyltransferase, atherosclerosis, and cardiovascular disease: triggering oxidative stress within the plaque. Circulation. 2005;112(14):2078–80. https://doi.org/10.1161/CIRCULATIONAHA.105.571919Search in Google Scholar

23. Ndrepepa G, Kastrati A. Gamma-glutamyl transferase and cardiovascular disease. Ann Transl Med. 2016;4(24):481. https://doi.org/10.21037/atm.2016.12.27Search in Google Scholar

24. Zheng MQ, Tang K, Zimmerman MC, Liu L, Xie B, Rozanski GJ. Role of gamma-glutamyl transpeptidase in redox regulation of K+ channel remodeling in postmyocardial infarction rat hearts. Am J Physiol Cell Physiol. 2009;297(2):C253–62. https://doi.org/10.1152/ajpcell.00634.2008Search in Google Scholar

25. Terekhina NA, Terekhin GA, Zhidko EV, Goryacheva OG. Oxidative modification of proteins, permeability of erythrocyte membranes and activity gamma-glutamiltranspeptidase in various intoxications. Medical science and education of Ural. 2019;20(4):78–82. Russian.Search in Google Scholar

26. Lee DH, Silventoinen K, Hu G, Jacobs DR Jr, Jousilahti P, Sundvall J, et al. Serum gamma-glutamyltransferase predicts non-fatal myocardial infarction and fatal coronary heart disease among 28,838 middle-aged men and women. Eur Heart J. 2006;27(18):2170–6. https://doi.org/10.1093/eurheartj/ehl086Search in Google Scholar

27. Ruttmann E, Brant LJ, Concin H, Diem G, Rapp K, Ulmer H. Gamma-glutamyltransferase as a risk factor for cardiovascular disease mortality: an epidemiological investigation in a cohort of 163,944 Austrian adults. Circulation. 2005;112(14):2130–7. https://doi.org/10.1161/CIRCULATIONAHA.105.552547Search in Google Scholar

28. Emdin M, Passino C, Michelassi C, Titta F, L’abbate A, Donato L, et al. Prognostic value of serum gamma-glutamyl transferase activity after myocardial infarction. Eur Heart J. 2001;22(19):1802–7. https://doi.org/10.1053/euhj.2001.2807Search in Google Scholar

29. Karlson BW, Wiklund O, Hallgren P, Sjölin M, Lindqvist J, Herlitz J. Ten-year mortality amongst patients with a very small or unconfirmed acute myocardial infarction in relation to clinical history, metabolic screening and signs of myocardial ischaemia. J Intern Med. 2000;247(4):449–56. https://doi.org/10.1046/j.1365-2796.2000.00679.xSearch in Google Scholar

30. Ulus T, Yildirir A, Sade LE, Temiz A, Polat E, Bozbaş H, et al. Serum gamma-glutamyl transferase activity: new high-risk criteria in acute coronary syndrome patients? Coron Artery Dis. 2008;19(7):489–95. https://doi.org/10.1097/MCA.0b013e32830eab8cSearch in Google Scholar

31. Strasak AM, Kelleher CC, Klenk J, Brant LJ, Ruttmann E, Rapp K, et al. Longitudinal change in serum gamma-glutamyltransferase and cardiovascular disease mortality: a prospective population-based study in 76,113 Austrian adults. Arterioscler Thromb Vasc Biol. 2008;28(10):1857–65. https://doi.org/10.1161/ATVBAHA.108.170597Search in Google Scholar

32. Franzini M, Paolicchi A, Fornaciari I, Ottaviano V, Fierabracci V, Maltinti M, et al. Cardiovascular risk factors and gamma-glutamyltransferase fractions in healthy individuals. Clin Chem Lab Med. 2010;48(5):713–7. https://doi.org/10.1515/CCLM.2010.125Search in Google Scholar

33. Sharma A, Fonarow GC, Butler J, Ezekowitz JA, Felker GM. Coenzyme Q10 and Heart Failure: A State-of-the-Art Review. Circ Heart Fail. 2016;9(4):e002639. https://doi.org/10.1161/CIRCHEARTFAILURE.115.002639Search in Google Scholar

34. Tereshchenko SN, Zhirov IV, Nasonova SN, Nikolaeva OA, Ledyakhova MV. Pathophysiology of acute heart failure. What’s new? Russian Journal of Cardiology. 2016;9(137):52–64. Russian. https://doi.org/10.15829/1560-4071-2016-9-52-64Search in Google Scholar

35. Irving BA, Lanza IR, Henderson GC, Rao RR, Spiegelman BM, Nair KS. Combined training enhances skeletal muscle mitochondrial oxidative capacity independent of age. J Clin Endocrinol Metab. 2015;100(4):1654–63. https://doi.org/10.1210/jc.2014-3081Search in Google Scholar

36. Paolicchi A, Emdin M, Ghliozeni E, Ciancia E, Passino C, Popoff G, et al. Images in cardiovascular medicine. Human atherosclerotic plaques contain gamma-glutamyl transpeptidase enzyme activity. Circulation. 2004;109(11):1440. https://doi.org/10.1161/01.CIR.0000120558.41356.E6Search in Google Scholar

37. Xue J, Huang H, Zhu C. GW28-e1203 ABCG1 attenuates Oxidative Stress Induced by TNF-α through the inhibition of NADPH oxidase and the upregulation of antioxidant enzymes in endothelial cells. J Am Coll Cardiol. 2018;70(16S):C46–7. https://doi.org/10.1016/j.jacc.2017.07.160Search in Google Scholar

38. Franssen C, Chen S, Unger A, Korkmaz HI, De Keulenaer GW, Tschöpe C, et al. Myocardial Microvascular Inflammatory Endothelial Activation in Heart Failure With Preserved Ejection Fraction. JACC Heart Fail. 2016;4(4):312–24. https://doi.org/10.1016/j.jchf.2015.10.007Search in Google Scholar

39. Harouki N, Nicol L, Remy-Jouet I, Henry JP, Dumesnil A, Lejeune A, et al. The IL-1β Antibody Gevokizumab Limits Cardiac Remodeling and Coronary Dysfunction in Rats With Heart Failure. JACC Basic Transl Sci. 2017;2(4):418–30. https://doi.org/10.1016/j.jacbts.2017.06.005Search in Google Scholar

40. Li H, Horke S, Förstermann U. Vascular oxidative stress, nitric oxide and atherosclerosis. Atherosclerosis. 2014;237(1):208–19. https://doi.org/10.1016/j.atherosclerosis.2014.09.001Search in Google Scholar

41. Ghafourian K, Shapiro JS, Goodman L, Ardehali H. Iron and Heart Failure: Diagnosis, Therapies, and Future Directions. JACC Basic Transl Sci. 2020;5(3):300–13. https://doi.org/10.1016/j.jacbts.2019.08.009Search in Google Scholar

42. Terekhina NA, Petrovich YuA. Free radical oxidation and antioxidant system. Perm; 2005. p. 1–57. Russian.Search in Google Scholar

43. Kennedy DJ, Fan Y, Wu Y, Pepoy M, Hazen SL, Tang WH. Plasma ceruloplasmin, a regulator of nitric oxide activity, and incident cardiovascular risk in patients with CKD. Clin J Am Soc Nephrol. 2014;9(3):462–7. https://doi.org/10.2215/CJN.07720713Search in Google Scholar

44. Jenkins DJA, Spence JD, Giovannucci EL, Kim YI, Josse R, Vieth R, et al. Supplemental Vitamins and Minerals for CVD Prevention and Treatment. Am Coll Cardiol. 2018;71(22):2570–84. https://doi.org/10.1016/j.jacc.2018.04.020Search in Google Scholar

45. Rosano GM, Vitale C. Metabolic Modulation of Cardiac Metabolism in Heart Failure. Card Fail Rev. 2018;4(2):99–103. https://doi.org/10.15420/cfr.2018.18.2Search in Google Scholar

46. Molyneux SL, Florkowski CM, George PM, Pilbrow AP, Frampton CM, Lever M, et al. Coenzyme Q10: an independent predictor of mortality in chronic heart failure. J Am Coll Cardiol. 2008;52(18):1435–41. https://doi.org/10.1016/j.jacc.2008.07.044Search in Google Scholar

47. Ruiz Rejón F, Martín-Peña G, Granado F, Ruiz-Galiana J, Blanco I, Olmedilla B. Plasma status of retinol, alpha- and gamma-tocopherols, and main carotenoids to first myocardial infarction: case control and follow-up study. Nutrition. 2002;18(1):26–31. https://doi.org/10.1016/s0899-9007(01)00683-9Search in Google Scholar

48. Terekhina NA, Goryacheva OG. Influence of heart failure severity on the content of alpha-tocopherol in erythrocytes of blood in myocardial infarction. Medical alphabet. 2015;1(2):52–3. Russian.Search in Google Scholar

49. Keaney JF Jr, Gaziano JM, Xu A, Frei B, Curran-Celentano J, Shwaery GT, et al. Low-dose alpha-tocopherol improves and high-dose alpha-tocopherol worsens endothelial vasodilator function in cholesterol-fed rabbits. J Clin Invest. 1994;93(2):844–51. https://doi.org/10.1172/JCI117039Search in Google Scholar

50. Stocker R. The ambivalence of vitamin E in atherogenesis. Trends Biochem Sci. 1999;24(6):219–23. https://doi.org/10.1016/s0968-0004(99)01404-8Search in Google Scholar

51. Lonn E, Bosch J, Yusuf S, Sheridan P, Pogue J, Arnold JM, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA. 2005;293(11):1338–47. https://doi.org/10.1001/jama.293.11.1338Search in Google Scholar

52. Fiarresga AJ, Feliciano J, Fernandes R, Martins A, Pelicano N, Timóteo AT, et al. Relationship between coronary disease and subclinical hypothyroidism: an angiographic study. Rev Port Cardiol. 2009;28(5):535–43.Search in Google Scholar

53. Depalma RG, Hayes VW, Chow BK, Shamayeva G, May PE, Zacharski LR. Ferritin levels, inflammatory biomarkers, and mortality in peripheral arterial disease: a substudy of the Iron (Fe) and Atherosclerosis Study (FeAST) Trial. J Vasc Surg. 2010;51(6):1498–503. https://doi.org/10.1016/j.jvs.2009.12.068Search in Google Scholar

54. Shreĭder EV, Shakhnovich Rm, Kaznacheeva EI, Bosykh EG, Tkachev GA, Ruda MIa. Comparative dynamics of markers of inflammation and NT-proBNP in different variants of treatment of patients with ACS. Kardiologiia. 2008;48(8):20–7. Russian.Search in Google Scholar

55. Okuneva GN, Chernyavsky AM, Levicheva EN, Loginova IYu, Volkov AM, Trunova VA, et al. Content of microelements in left ventricular myocardium of patients with ischemic heart disease. Data of roentgenofluorescent analysis with the use of synchrotron irradiation. Kardiologiia. 2006;46(10):13–7. Russian.Search in Google Scholar

56. Mladenka P, Hrdina R, Bobrovová Z, Semecky V, Vávrová J, Holecková M, et al. Cardiac biomarkers in a model of acute cate-cholamine cardiotoxicity. Hum Exp Toxicol. 2009;28(10):631–40. https://doi.org/10.1177/0960327109350665Search in Google Scholar

57. Jankowska EA, von Haehling S, Anker SD, Macdougall IC, Ponikowski P. Iron deficiency and heart failure: diagnostic dilemmas and therapeutic perspectives. Eur Heart J. 2013;34(11):816–29. https://doi.org/10.1093/eurheartj/ehs224Search in Google Scholar

58. Kazi TG, Afridi HI, Kazi N, Jamali MK, Arain MB, Sarfraz RA, et al. Distribution of zinc, copper and iron in biological samples of Pakistani myocardial infarction (1st, 2nd and 3rd heart attack) patients and controls. Clin Chim Acta. 2008;389(1–2):114–9. https://doi.org/10.1016/j.cca.2007.12.004Search in Google Scholar

59. Shokrzadeh M, Ghaemian A, Salehifar E, Aliakbari S, Saravi SS, Ebrahimi P. Serum zinc and copper levels in ischemic cardiomyopathy. Biol Trace Elem Res. 2009;127(2):116–23. https://doi.org/10.1007/s12011-008-8237-1Search in Google Scholar

60. Hoenig MR, Bianchi C, Sellke FW. Hypoxia inducible factor-1 alpha, endothelial progenitor cells, monocytes, cardiovascular risk, wound healing, cobalt and hydralazine: a unifying hypothesis. Curr Drug Targets. 2008;9(5):422–35. https://doi.org/10.2174/138945008784221215Search in Google Scholar

61. Lele S, Shah S, McCullough PA, Rajapurkar M. Serum catalytic iron as a novel biomarker of vascular injury in acute coronary syndromes. EuroIntervention. 2009;5(3):336–42. https://doi.org/10.4244/v5i3a53Search in Google Scholar

62. Qiao H, Li L, Qu ZC, May JM. Cobalt-induced oxidant stress in cultured endothelial cells: prevention by ascorbate in relation to HIF-1alpha. Biofactors. 2009;35(3):306–13. https://doi.org/10.1002/biof.43Search in Google Scholar

63. Bhagavan NV, Lai EM, Rios PA, Yang J, Ortega-Lopez AM, Shinoda H, et al. Evaluation of human serum albumin cobalt binding assay for the assessment of myocardial ischemia and myocardial infarction. Clin Chem. 2003;49(4):581–5. https://doi.org/10.1373/49.4.581Search in Google Scholar

64. Holme I, Aastveit AH, Hammar N, Jungner I, Walldius G. Uric acid and risk of myocardial infarction, stroke and congestive heart failure in 417,734 men and women in the Apolipoprotein MOrtality RISk study (AMORIS). J Intern Med. 2009;266(6):558–70. https://doi.org/10.1111/j.1365-2796.2009.02133.xSearch in Google Scholar

65. Nadkar MY, Jain VI. Serum uric acid in acute myocardial infarction. J Assoc Physicians India. 2008;56:759–62.Search in Google Scholar

66. Car S, Trkulja V. Higher serum uric acid on admission is associated with higher short-term mortality and poorer long-term survival after myocardial infarction: retrospective prognostic study. Croat Med J. 2009;50(6):559–66.Search in Google Scholar

67. Dan GA. Thyroid hormones and the heart. Heart Fail Rev. 2016;21(4):357–9. https://doi.org/10.1007/s10741-016-9555-6Search in Google Scholar

68. Coceani M, Iervasi G, Pingitore A, Carpeggiani C, L’Abbate A. Thyroid hormone and coronary artery disease: from clinical correlations to prognostic implications. Clin Cardiol. 2009;32(7):380–5. https://doi.org/10.1002/clc.20574Search in Google Scholar

69. Yaman B, Cerit L, Günsel HK, Günsel A, Usalp S, Yüksek Ü, et al. Association between subclinical hypothyroidism and coronary artery disease. Progress in Nutrition. 2019;21(4):871–5. https://doi.org/10.23751/pn.v21i4.7979Search in Google Scholar

70. Chen YF, Redetzke RA, Said S, Beyer AJ, Gerdes AM. Changes in left ventricular function and remodeling after myocar-dial infarction in hypothyroid rats. Am J Physiol Heart Circ Physiol. 2010;298(1):H259–62. https://doi.org/10.1152/ajp-heart.00755.2009Search in Google Scholar

71. Wang W, Zhang L, Battiprolu PK, Fukushima A, Nguyen K, Milner K, et al. Malonyl CoA decarboxylase Inhibition improves cardiac function post-myocardial infarction. JACC Basic Transl Sci. 2019;4(3):385–400. doi.org/10.1016/j.jacbts.2019.02.003Search in Google Scholar

72. Freaney PM, Shah SJ, Khan SS. COVID-19 and Heart Failure With Preserved Ejection Fraction. JAMA. 2020;324(15):1499–1500. https://doi.org/10.1001/jama.2020.17445Search in Google Scholar

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