Skip to main content
SpringerLink
Log in

Antioxidant enzyme gene expression in congestive heart failure following mycardial infarction

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Increased oxidative stress and reduction in antioxidant enzymes have been suggested to be involved in the pathophysiology of congestive heart failure subsequent to myocardial infarction (MI). The objective of the present study was to characterize changes in the mRNA abundance and protein levels for the enzymatic antioxidants, superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase during the sequelae of congestive heart failure in rats. MI was produced by the ligation of the left coronary artery and hearts from controls and 1, 4 and 16 week PMI groups were analyzed. Losartan treatment (2 mg/ml in drinking water, daily) was started at 4 weeks and continued for 12 weeks. The mRNA levels for SOD were reduced by about 40% at 1-week PMI, were near to the control levels at 4-week PMI and at 16 weeks PMI, the levels were reduced by about 73% below the controls. GSHPx mRNA levels remained unchanged at all time points. The mRNA levels for catalase remained unchanged at 1 and 4 weeks PMI and were significantly reduced by about 44% at 16 weeks PMI as compared to the controls. The protein levels for MnSOD, CuZnSOD, GSHPx at 1 and 16 weeks remained unchanged in treated and untreated PMI groups. However, the protein levels for catalase was significantly increased in the control and PMI groups treated with Losartan. It is concluded that changes in the SOD and catalase activities during severe heart failure correlated with changes in mRNA for these enzymes. The precise mechanism/s for the improvement in antioxidant reserve and protein levels after Losartan treatment is/are unclear at this time.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. McAlpine HM, Cobbe SM: Neuroendocrine changes in acute myocardial infarction. Am J Med 84: 61-66, 1988

    Google Scholar 

  2. Singh RB, Niaz MA, Rastogi SS, Rastogi S: Usefulness of antioxidant vitamins in suspected acute myocardial infarction (The Indian Experiment of Infarct Survival-3). Am J Cardiol 77: 232-236, 1996

    Google Scholar 

  3. Keith M, Geranmayegan A, Sole MJ, Kurian R, Robinson A, Omran AS, Jeejeebhoy KN: Increased oxidative stress in patients with congestive heart failure. J Am Coll Cardiol 31: 1352-1356, 1998

    Google Scholar 

  4. Hill MF, Singal PK: Right and left myocardial antioxidant responses during heart failure subsequent to myocardial infarction. Circulation 96: 2414-2420, 1997

    Google Scholar 

  5. Palace VP, Hill MF, Farahmand F, Singal PK: Mobilization of antioxidant vitamin pools and hemodynamic function following myocardial infarction. Circulation 99: 121-126, 1999

    Google Scholar 

  6. Kaul N, Siveski-Iliskovic N, Hill M, Slezak J, Singal PK: Free radicals and the heart. J Pharmacol Toxicol Meth 30: 55-67, 1993

    Google Scholar 

  7. Serdar A, Yesilbursa D, Serdar Z, Dirican M, Turel B, Cordan J: Relation of functional capacity with the oxidative stress and antioxidants in chronic heart failure. Congest Heart Fail 7: 309-311, 2001

    Google Scholar 

  8. Sia YT, Parker TG, Liu P, Tsoporis JN, Adam A, Rouleau JL: Improved post-myocardial infarction survival with probucol in rats: Effects on left ventricular function, morphology, cardiac oxidative stress and cytokine expression. J Am Coll Cardiol 39: 148-156, 2002

    Google Scholar 

  9. Khaper N, Singal PK: Effects of afterload reducing drugs on the pathogenesis of antioxidant changes and congestive heart failure in rats. J Am Coll Cardiol 29: 856-861, 1997

    Google Scholar 

  10. Pitt B, Segal R, Martinez FA, Meurers G, Cowley AJ, Thomas I, Deedwania PC, Ney DE, Snavely DB, Chang PI: on behalf of ELITE Investigators. Randomised trial of Losartan vs. captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet 349: 747-752, 1997

    Google Scholar 

  11. Schieffer B, Wirgner A, Meybrunn M, Seitz S, Holtz J, Riede UN, Drexler H: Comparative effects of chronic angiotensin converting enzyme inhibition and angiotensin II type 1 receptor blockade on cardiac remodelling after myocardial infarction in the rat. Circulation 88: 2273-2282, 1994

    Google Scholar 

  12. Johns TNP, Olson BJ: Experimental myocardial infarction: I. A method of coronary occlusion in small animals. Ann Surg 140: 675-682, 1954

    Google Scholar 

  13. Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ: Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18: 5294-5299, 1979

    Google Scholar 

  14. Cowan DB, Weisel RD, Williams WG, Mickle DA: The regulation of glutathione peroxidase gene expression by oxygen tension in cultured human cardiomyocytes. J Mol Cell Cardiol 24: 423-433, 1992

    Google Scholar 

  15. Xiang K, Cox NJ, Hallewell RA, Bell GI: Multiple Taq I RFLPs at the human manganese superoxide dismutase (SOD2) locus on chromosome 6. Nucleic Acids Res 15: 7654, 1987

    Google Scholar 

  16. Quan F, Korneluk RG, Tropak MB, Gravel RA: Isolation and characterization of the human catalase gene. Nucleic Acids Res 14: 5321-5335, 1986

    Google Scholar 

  17. Tiemeier DC, Tilghman SM, Leder P: Purification and cloning of a mouse ribosomal gene fragment in coliphage lambda. Gene 2: 173-191, 1977

    Google Scholar 

  18. Khaper N, Rigatto C, Seneviratne C, Li T, Singal PK: Chronic treatment with propranolol induces antioxidant changes and protects against ischemia reperfusion injury. J Mol Cell Cardiol 29: 3335-3344, 1997

    Google Scholar 

  19. Hurt J, Hsu JL, Dougall WC, Visner GA, Burr IM, Nick HS: Multiple mRNA species generated by alternate polyadenylation from the rat manganese superoxide dismutase gene. Nucleic Acids Res 20: 2985-2990, 1992

    Google Scholar 

  20. Lowry OH, Rosenbrough NT, Farr AL et al.: Protein measurements with the Folin phenol reagent. J Biol Chem 193: 265-275, 1951

    Google Scholar 

  21. Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680-685, 1970

    Google Scholar 

  22. Khaper N, Singal PK: Modulation of oxidative stress by a selective inhibition of angiotensin II type 1 receptors in MI rats. J Am Coll Cardiol 37: 1461-1466, 2001

    Google Scholar 

  23. Dieterich S, Bieligk U, Beulich K, Hasenfuss G, Prestle J: Gene expression of antioxidative enzymes in the human heart: Increased expression of catalase in the end stage failing heart. Circulation 101: 33-39, 2000

    Google Scholar 

  24. Baumer AT, Flesch M, Wang X, Shen Q, Feuerstein GZ, Bohm M: Antioxidative enzymes in human hearts with idiopathic dilated cardiomyopathy. J Mol Cell Cardiol 32: 121-130, 2000

    Google Scholar 

  25. Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ Jr, Cuddy TE, Davis BR, Geltman EM, Goldman S, Flaker GC et al. on behalf of the SAVE Investigators: Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: Results of the Survival and Ventricular Enlargement trial (SAVE). N Engl J Med 327: 669-677, 1992

    Google Scholar 

  26. Cohn JN, Johnson G, Ziesche S, Cobb F, Francis G, Tristani F, Smith R, Dunkman WB, Loeb H, Wong M et al.: A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 325: 303-310, 1991

    Google Scholar 

  27. Gohlke P, Linz W, Scholkens BA, Kuwer I, Bartenbach S, Schnell A, Unger T: Angiotensin-converting enzyme inhibition improves cardiac function: Role of bradykinin. Hypertension 23: 411-418, 1994

    Google Scholar 

  28. Martorana PA, Linz W, Scholkens BA: Does bradykinin play a role in the cardiac anti-ischemic effect of the ACE-inhibitors? Basic Res Cardiol. 86: 293-296, 1991

    Google Scholar 

  29. Linz W, Scholkens BA: A specific B2-bradykinin receptor antagonist HOE 140 abolishes the antihypertrophic effect of ramipril. Br J Pharmacol 105: 771-772, 1992

    Google Scholar 

  30. Schror K: Role of prostaglandins in the cardiovascular effects of bradykinin and angiotensin converting enzyme inhibitors in heart failure. J Cardiovasc Pharmacol 20: 68-73, 1992

    Google Scholar 

  31. Rump LC, Oberhauser V, Schwertfeger E, Schollmeyer P: Experimental evidence to support ELITE. Lancet 351: 644-645, 1998

    Google Scholar 

  32. Rajagopalan S, Kurz S, Muenzel T, Tarpey M, Freeman BA, Griendling KK, Harrison DG: Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest 97: 1916-1923, 1996

    Google Scholar 

  33. Griendling KK, Minieri CA, Ollerenshaw JD Alexander RW: Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res 74: 1141-1148, 1994

    Google Scholar 

  34. Aizawa T, Ishizaka N, Usui S, Ohashi N, Ohno M, Nagai R: Angiotensin II and catecholamines increase plasma levels of 8-epi-prostaglandin F (2 alpha) with different pressor dependencies in rats. Hypertension 39: 149-154, 2002

    Google Scholar 

  35. Yasunari K, Maeda K, Nakamura M, Yoshikawa J: Pressure promotes angiotensin II-mediated migration of human coronary smooth muscle cells through increase in oxidative stress. Hypertension 39: 433-437, 2002

    Google Scholar 

  36. Puig JG, Mateos F, Buno A, Ortega R, Rodriguez F, Dal-Re R: Effect of eprosartan and Losartan on uric acid metabolism in patients with essential hypertension. J Hypertens 17: 1033-1039, 1999

    Google Scholar 

  37. Kedziora-Kornatowska K: Effects of angiotensin convertase inhibitors and AT1 angiotensin receptor antagonists on the development of oxidative stress in the kidney of diabetic rats. Clin Chim Acta 287: 19-27, 1999

    Google Scholar 

  38. Hornig B, Landmesser U, Kohler C, Ahlersmann D, Spiekermann S, Christoph A, Tatge H, Drexler H: Comparative effects of ACE inhibition and angiotensin II type 1 receptor antagonism on bioavailability of nitric oxide in patients with coronary artery disease: Role of superoxide dismutase. Circulation 103: 799-805, 2001

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Canada

    N. Khaper, K. Kaur, T. Li, F. Farahmand & P.K. Singal

  2. Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    N. Khaper, K. Kaur, T. Li, F. Farahmand & P.K. Singal

Authors
  1. N. Khaper
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Kaur
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F. Farahmand
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P.K. Singal
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khaper, N., Kaur, K., Li, T. et al. Antioxidant enzyme gene expression in congestive heart failure following mycardial infarction. Mol Cell Biochem 251, 9–15 (2003). https://doi.org/10.1023/A:1025448908694

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1025448908694

Search

Navigation