Current Hypertension Reports

, Volume 5, Issue 3, pp 215–220

Oxidative stress and heart disease: Cardiac dysfunction, nutrition, and gene therapy

  • Elliott J. F. Cantor
  • Enrico V. Mancini
  • Rishi Seth
  • Xing-Hai Yao
  • Thomas Netticadan


Oxidative stress is defined as the imbalance between the generation of reactive oxygen species and antioxidant defense mechanisms. The cardiovascular system is a major target for reactive oxygen species. Cardiomyocytes and the vasculature of the heart can be severely damaged as a result of oxidative stress. In this paper, we discuss recent findings with respect to the role of oxidative stress in heart disease. The efficacies of treatments with vitamins and wine-derived compounds, as well as innovative gene therapeutic experiments that may potentially alleviate oxidative stress-induced disease, are also discussed.


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References and Recommended Reading

  1. 1.
    Lang D: Cardiac hypertrophy and oxidative stress: a leap of faith or stark reality? Heart 2002, 87:316–317.PubMedCrossRefGoogle Scholar
  2. 2.
    Dhalla NS, Temsah RM, Netticadan T: Role of oxidative stress in cardiovascular disease. J Hypertens 2000, 18:655–673.PubMedCrossRefGoogle Scholar
  3. 3.
    Searles CD: The nitric oxide pathway and oxidative stress in heart failure. Congest Heart Fail 2002, 8:142–147.PubMedGoogle Scholar
  4. 4.
    Blokhina O, Virolainen E, Fagerstedt KV: Antioxidants, oxidative damage and oxygen deprivation stress: a review. Ann Bot (Lond) 2002, 91:179–194.CrossRefGoogle Scholar
  5. 5.
    Choudhary G, Dudley S: Heart failure, oxidative stress, and ion channel modulation. Congest Heart Fail 2002, 8:148–155.PubMedGoogle Scholar
  6. 6.
    Guzik TJ, West NEJ, Pillai R, et al.: Nitric oxide modulates superoxide release and peroxynitrite formation in human blood vessels. Hypertension 2002, 39:1088–1094.PubMedCrossRefGoogle Scholar
  7. 7.
    Hingtgen SD, Davisson RL: Gene therapeutic approaches to oxidative stress-induced cardiac disease: principles, progress, and prospects. Antioxid Redox Signal 2001, 3:433–49.PubMedCrossRefGoogle Scholar
  8. 8.
    Lefer DJ, Granger DN: Oxidative stress and cardiac disease. Am J Med 2000, 109:315–323.PubMedCrossRefGoogle Scholar
  9. 9.
    Engelhardt JF: Redox-mediated gene therapies for environmnetal injury: approaches and concepts. Antioxid Redox Signal 1999, 1:5–27.PubMedCrossRefGoogle Scholar
  10. 10.
    Chen Z, Siu B, Ho YS, et al.: Overexpression of Mn-SOD protects against myocardial ischemia/reperfusion injury in transgenic mice. J Mol Cell Cardiol 1998, 30:2281–2289.PubMedCrossRefGoogle Scholar
  11. 11.
    Yang L, Quan S, Abraham NG: Retrovirus-mediated HO gene transfer into endothelial cells protects against oxidantinduced injury. Am J Physiol 1999, 277:L127-L133.PubMedGoogle Scholar
  12. 12.
    Melo LG, Agrawal R, Zhang L, et al.: Gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene. Circulation 2002, 105:602–607. Novel concept of preventative myocardial gene therapy using adenoassociated virus-mediated delivery of heme oxygenase gene.PubMedCrossRefGoogle Scholar
  13. 13.
    Bers DM: Cardiac excitation-contraction coupling. Nature 2002, 415:198–205.PubMedCrossRefGoogle Scholar
  14. 14.
    Tappia PS, Hata T, Hozaima L, et al.: Role of oxidative stress in catecholamine-induced changes in cardiac sarcolemmal Ca2+ transport. Arch Biochem Biophys 2001, 387:85–92. Oxidative stress-induced defects in sarcolemmal Ca2+ transport contribute to abnormal cardiac performance.PubMedCrossRefGoogle Scholar
  15. 15.
    Netticadan T, Temsah R, Osada M, Dhalla NS: Status of Ca2+/ calmodulin protein kinase phosphorylation of cardiac SR proteins in ischemia-reperfusion. Am J Physiol 1999, 277:C384-C391.PubMedGoogle Scholar
  16. 16.
    Temsah RM, Netticadan T, Chapman D, et al.: Alterations in sarcoplasmic reticulum function and gene expression in ischemicreperfused rat heart. Am J Physiol 1999, 277:H584-H594.PubMedGoogle Scholar
  17. 17.
    Itoh S, Yanagishita T, Aoki S, et al.: Generation of free radicals and the damage done to the sarcoplasmic reticulum during reperfusion injury following brief ischemia in the canine heart. Jpn Circ J 1999, 63:373–378.PubMedCrossRefGoogle Scholar
  18. 18.
    Sharma R, Davidoff MN: Oxidative stress and endothelial dysfunction in heart failure. Congest Heart Fail 2002, 8:165–172.PubMedGoogle Scholar
  19. 19.
    Duffy SJ, Gokce N, Holbrook M, et al.: Effect of ascorbic acid treatment on conduit vessel endothelial dysfunction in patients with hypertension. Am J Physiol Heart Circ Physiol 2001, 280:H528-H534.PubMedGoogle Scholar
  20. 20.
    Heart Protection Study Collaborative Group: MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20 536 high-risk individuals: a randomized placebo-controlled trial. Lancet 2002, 360:23–33.CrossRefGoogle Scholar
  21. 21.
    Yusuf S, Dagenais G, Pogue J, et al.: Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000, 342:154–160. Lack of cardioprotection of vitamin E treatment in patients with myocardial infarction or any other cardiovascular cause.PubMedCrossRefGoogle Scholar
  22. 22.
    Meagher EA, Barry OP, Lawson JA, et al.: Effects of vitamin E on lipid peroxidation in healthy persons. JAMA 2001, 285:1178–1182.PubMedCrossRefGoogle Scholar
  23. 23.
    Huang H-Y, Appel LJ, Croft KD, et al.: Effects of vitamin C and vitamin E on in vivo lipid peroxidation: results of a randomized controlled trial. Am J Clin Nutr 2002, 76:549–555.PubMedGoogle Scholar
  24. 24.
    Salonen JT, Nyyssönen K, Salonen R, et al.: Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3-year progression of carotid atherslerosis. J Intern Med 2000, 248:377–386.PubMedCrossRefGoogle Scholar
  25. 25.
    Iannuzzi A, Celentano E, Salvatore P, et al.: Dietary and circulating antioxidant vitamins in relation to carotid plaques in middle-aged women. Am J Clin Nutr 2002, 76:582–587.PubMedGoogle Scholar
  26. 26.
    Sethi R, Takeda N, Nagano M, Dhalla NS: Beneficial effects of vitamin E treatment in acute myocardial infarction. J Cardiovasc Pharmacol Ther 2000, 5:51–58.PubMedGoogle Scholar
  27. 27.
    Venditti P, Masullo P, Di Meo S, Agnisola C: Protection against ischemia-reperfusion induced oxidative stress by vitamin E treatment. Arch Physiol Biochem 1999, 107:27–34.PubMedCrossRefGoogle Scholar
  28. 28.
    Coombes JS, Powers SK, Demirel HA, et al.: Effect of combined supplementation with vitamin E and alpha-lipoic acid on myocardial performance during in vivo ischaemia-reperfusion. Acta Physiol Scand 2000, 169:261–269.PubMedCrossRefGoogle Scholar
  29. 29.
    Coombes JS, Powers SK, Hamilton KL, et al.: Improved cardiac performance after ischemia in aged rats supplemented with vitamin E and alpha-lipoic acid. Am J Physiol Regul Integr Comp Physiol 2000, 279:R2149-R2155.PubMedGoogle Scholar
  30. 30.
    Bernátová I, Pechánová O, Babál P, et al.: Wine polyphenols improve cardiovascular remodeling and vascular function in NO-deficient hypertension. Am J Physiol Heart Circ Physiol 2002, 282:H942-H948.PubMedGoogle Scholar
  31. 31.
    Jamroz A, Beltowski J: Antioxidant capacity of selected wines. Med Sci Monit 2001, 7:1198–1202.PubMedGoogle Scholar
  32. 32.
    Sato M, Maulik G, Ray PS, et al.: Cardioprotective Effects of grape seed proanthocyanidin against ischemic reperfusion injury. J Mol Cell Cardiol 1999, 31:1289–1297.PubMedCrossRefGoogle Scholar
  33. 33.
    Pataki T, Bak I, Kovacs P, et al.: Grape seed proanthocyanidins improved cardiac recovery during reperfusion after ischemia in isolated rat hearts. Am J Clin Nutr 2002, 75:894–899.PubMedGoogle Scholar
  34. 34.
    Ray PS, Maulik G, Cordis GA, et al.: The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury. Free Radic Biol Med 1999, 27:160–169.PubMedCrossRefGoogle Scholar
  35. 35.
    Sato M, Ray PS, Maulik G, et al.: Myocardial protection with red wine extract. J Cardiovasc Pharmacol 2000, 35:263–268.PubMedCrossRefGoogle Scholar
  36. 36.
    Hale SL, Kloner RA: Effects of resveratrol, a flavinoid found in red wine, on infarct size in an experimental model of ischemia/reperfusion. J Stud Alcohol 2001, 62:730–735.PubMedGoogle Scholar
  37. 37.
    Hung LM, Chen JK, Huang SS, et al.: Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. Cardiovasc Res 2000, 47:549–555. Evidence for resveratrol as a potent antiarrhythmic agent with cardioprotective properties in an in vivo model of I/R.PubMedCrossRefGoogle Scholar
  38. 38.
    Bertelli AA, Migliori M, Panichi V, et al.: Oxidative stress and inflammatory reaction modulation by white wine. Ann N Y Acad Sci 2002, 957:295–301.PubMedGoogle Scholar
  39. 39.
    Cui J, Cordis GA, Tosaki A, et al.: Reduction of Myocardial Ischemia Referfusion Injury with Regular consumption of grapes. Ann N Y Acad Sci 2002, 957:302–307.PubMedCrossRefGoogle Scholar
  40. 40.
    Woo YJ, Zhang JC, Vijayasarathy C, et al.: Recombinant adenovirus-mediated cardiac gene transfer of superoxide dismutase and catalase attenuates postischemic contractile dysfunction. Circulation 1998, 98(19 Suppl):II255–261.PubMedGoogle Scholar
  41. 41.
    Li Q, Bolli R, Qiu Y, et al.: Gene therapy with extracellular superoxide dismutase attenuates myocardial stunning in conscious rabbits. Circulation 1998, 98:1438–1448.PubMedGoogle Scholar
  42. 42.
    Li Q, Bolli R, Qiu Y, et al.: Gene therapy with extracellular superoxide dismutase protects conscious rabbits against myocardial infarction. Circulation 2001, 103:1893–1898. Evidence of cardioprotection against myocardial infarction using adenoviral-mediated delivery of antioxidant Ec-SOD to the heart.PubMedGoogle Scholar
  43. 43.
    Abunasra HJ, Smolenski RT, Morrison K, et al.: Efficacy of adenoviral gene transfer with manganese superoxide dismutase and endothelial nitric oxide synthase in reducing ischemia and reperfusion injury. Eur J Cardiothorac Surg 2001, 20:153–158.PubMedCrossRefGoogle Scholar
  44. 44.
    Yoshida T, Maulik N, Engelman RM, et al.: Targeted disruption of the mouse Sod I gene makes the hearts vulnerable to ischemic reperfusion injury. Circ Res 2000, 86:264–269.PubMedGoogle Scholar
  45. 45.
    Wang P, Chen H, Qin H, et al.: Overexpression of human copper, zinc-superoxide dismutase (SOD1) prevents postischemic injury. Proc Natl Acad Sci U S A 1998, 95:4556–4560.PubMedCrossRefGoogle Scholar
  46. 46.
    Zhu HL, Stewart AS, Taylor MD, et al.: Blocking free radical production via adenoviral gene transfer decreases cardiac ischemia-reperfusion injury. Mol Ther 2000, 2:470–475.PubMedCrossRefGoogle Scholar
  47. 47.
    Svensson EC, Marshall DJ, Woodard K, et al.: Efficient and stable transduction of cardiomyocytes after intramyocardial injection or intracoronary perfusion with recombinant adeno-associated virus vectors. Circulation 1999, 99:201–205.PubMedGoogle Scholar
  48. 48.
    Sakoda T, Kasahara N, Hamamori Y, Kedes L: A high-titer lentiviral production system mediates efficient transduction of differentiated cells including beating cardiac myocytes. J Mol Cell Cardiol 1999, 31:2037–2047.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2003

Authors and Affiliations

  • Elliott J. F. Cantor
  • Enrico V. Mancini
  • Rishi Seth
  • Xing-Hai Yao
  • Thomas Netticadan
    • 1
  1. 1.Institute of Cardiovascular SciencesSt. Boniface General Hospital Research CentreWinnipegCanada

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