Skip to main content
SpringerLink
Log in

The Role of Free Radicals as Mediators of Endothelial Cell Injury in Hyperhomocysteinemia

  • Published:
Irish Journal of Medical Science Aims and scope Submit manuscript

Abstract

Hyperhomocysteinemia has been suggested as a potent new risk factor for premature cardiovascular disease. Homocsyteine can induce endothelial cell injury but the mechanism is not understood. The purpose of this study was to evaluate the role of free radicals as potential causes of endothelial cell injury in a case-control study of obligate heterozygotes for cystathionine ß-synthase deficiency. Firstly, free radical production as measured by neutrophil chemiluminescence in obligate heterozygotes for cystathionine ß-synthase deficiency was compared with age- and sex-matched normal subjects. Secondly, the response of the cellular antioxidant system was examined by measuring the enzymes Superoxide dismutase and glutathione peroxidase, their cofactors (selenium, copper), vitamin E and vitamin A in heterozygotes and normal subjects. Analyses of neutrophil chemiluminescence, vitamin A and E, glutathione peroxidase, selenium and copper showed no difference between heterozygotes and controls. While Superoxide dismutase activity was higher in heterozygotes than normal subjects, the difference did not reach statistical significance and the hypothesis of excess free radical production as a mechanism of injury was not confirmed. However, further examination of Superoxide dismutase activity in a larger number of subjects would be of interest.

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. Mudd, S. H., Levy, H. L., Skovby, F. Disorders of Transulfura- tion. In: Scriver, C., Beaudet, A. L., Sly, W. S., Valle, D., Eds. The Metabolic Basis of Inherited Disease. 6th Edit. McGraw-Hill: New York, 1989: pp. 693–734.

    Google Scholar 

  2. Boers, G. H., Smals, A. G., Trijbels, F. J.et al. Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease. N. Engl. J. Med. 1985: 313, 709–15.

    PubMed  CAS  Google Scholar 

  3. Brattstrom, L. E., Hardebo, I.E., Hultberg, B. L. Moderate homocysteinemia - a possible risk factor for arteriosclerotic cere- brovascular disease. Stroke 1984: 15, 1012–6.

    PubMed  CAS  Google Scholar 

  4. Clarke, R., Daly, L., Robinson, K., Naughten, E., Cahalane, S., Fowler, B., Graham, I. Hyperhomosysteinemia: an independent risk factor for vascular disease. N. Engl. J. Med. 1991: 324, 1149–55.

    PubMed  CAS  Google Scholar 

  5. Malinow, M. R., Kang, S. S., Taylor, L. M.et al. Prevalence of hyperhomocyst(e)inemia in patients with peripheral arterial occlusive disease. Circulation 1989: 79, 1180–8.

    CAS  Google Scholar 

  6. Harker, L. A., Slichter, S. J., Scott, C. R., Ross, R. Homocysteinemia, vascular injury and arterial thrombosis. N. Engl. J. Med. 1974: 291, 537–43.

    PubMed  CAS  Google Scholar 

  7. McCully, K. S. Homocysteine theory of arteriosclerosis; development and current status. Arteriosclerosis Rev. 1983: 11, 157–246.

    CAS  Google Scholar 

  8. Wall, R. T., Harlan, J. M., Harker, L. A., Striker, G. E. Homocys- teine-induced endothelial cell injury in vitro: a model for the study of vascular injury. Thromb. Res. 1989: 18, 113–21.

    Article  Google Scholar 

  9. Starkebaum, G., Harlan, J. M. Endothelial cell injury due to copper- catalyzed hydrogen peroxide generation from homocysteine. J. Clin. Invest. 1986: 77, 1370–76.

    Article  PubMed  CAS  Google Scholar 

  10. Parthasarathy, S. Oxidation of low density lipoprotein by thiol compounds leads to its recognition by the acetyl LDL receptor. Biochim. Biophys. Acta 1987: 917, 337–40.

    PubMed  CAS  Google Scholar 

  11. Panganamala, R. V., Karpen, C.W. Merola, A. J. Peroxide mediated effects of homocysteine on arterial prostacyclin synthesis. Prost. Leuk. Med. 1986: 22, 349–56.

    Article  CAS  Google Scholar 

  12. Clarke, R., Fitzgerald, D., O’Brien, C. O’Farrell, C., Roche, G., Parker, R. A., Graham, I. Hyperhomocysteinemia: a risk factor for extracranial carotid artery atherosclerosis. Ir. J. Med. Sci. 1992 (in press).

  13. Frimpter, G. W. The disulfide of L-cysteine and L-homocysteine in urine of patients with cystinuria. J. Biol. Chem. 1961: 236, 51- 53.

    Google Scholar 

  14. Paglia, D. E., Valentine, W. N. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med. 1967: 70, 158–69.

    PubMed  CAS  Google Scholar 

  15. Gray, D. E., Lanfong, H. L., Wyman, J. F. An automated analysis for Superoxide dismutase activity. J. Analyt. Toxicol. 1985: 9, 36- 39.

    CAS  Google Scholar 

  16. Spallholtz, J. G., Collins, B. F., Schwartz, K. A single test tube method for fluorimetric microdetection of selenium. Bio. Organic Chem. 1978: 9, 453–9.

    Google Scholar 

  17. Vir, S. C, Love, A. H. G., Thompson, W. Serum and hair concentrations of copper during pregnancy. Am. J. Clin. Nutr. 1981: 34, 2382–8.

    PubMed  CAS  Google Scholar 

  18. Bieri, J. G., Tolliver, T. J., Catigani, G. L. Simultaneous determination of alpha-tochopherol and retinol in plasma by high pressure liquid chromatography. Am. J. Clin. Nutr. 1979: 32, 2143–9.

    PubMed  CAS  Google Scholar 

  19. Misra, H. P. Generation of Superoxide free radicals during the auto oxidation of thiols. J. Biol. Chem. 1974: 249, 2151–55.

    PubMed  CAS  Google Scholar 

  20. Zwart, J. H., Van Wolput, H. M. C., Van Der Cammen, J. C. M., Konigsberger, D. C. Accumulation and reactions of H2O2 during the copper ion catalyzed auto oxidation of cysteine in an alkaline medium. J. Mol. Catal. 1981: 11, 69–82.

    Article  CAS  Google Scholar 

  21. Saez, G., Thornally, P. J., Hill, H. A. O.et al. The production of free radicals during the auto oxidation of cysteine and their effect on isolated rat hepatocytes. Biochim. Biophys. Acta 1982: 719, 24- 30.

    PubMed  CAS  Google Scholar 

  22. Monacada, S. Prostacyclin and arterial wall biology. Atherosclero- sis 1982: 2, 193–207.

    Google Scholar 

  23. Moncada.S., Radonski, M. J., Palmer, R.M.J. Endothelium-derived relaxing factor: identification as nitric oxide and role in the control of vascular tone and platelet function. Biochem. Pharmacol. 1988: 37, 2495–2501.

    Article  PubMed  Google Scholar 

  24. Gryglewski, R. J., Palmer, R. M. J., Moncada, S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 1986: 320, 454–56.

    Article  PubMed  CAS  Google Scholar 

  25. McCall, T. B., Broughton-Smith, N. K., Palmer, R. M. J.et al. Synthesis of nitric oxide from L-arginine by neutrophils, release and interaction with Superoxide anions. Biochem. J. 1989: 261, 293–96.

    PubMed  CAS  Google Scholar 

  26. Murphy-Chutorian, D. R., Wexman, M. P., Grieco, A. J.et al. Methionine intolerance: a possible risk factor for coronary artery disease. J. Am. Coll. Cardiol. 1985: 6, 725–30.

    Article  PubMed  CAS  Google Scholar 

  27. Issraelson, B., Brattstrom, L. E., Hultberg, B. L. Homosysteinemia and myocardial infarction. Atherosclerosis 1988: 71, 227–33.

    Article  Google Scholar 

  28. Kang, S., Wong, P. E. K., Cook, H. Y.et al. Protein bound homocyst(e)ine: a possible risk factor for coronary artery disease. J. Clin. Invest. 1988: 77, 1482–6.

    Article  Google Scholar 

  29. Olszewski, A. J., Szostak, W. B. Homocysteine content of plasma proteins in ischaemic heart disease. Atherosclerosis 1988: 69, 109- 13.

    Article  PubMed  CAS  Google Scholar 

  30. Stryker, W. S., Kaplan, L. A., Stein, E. A.et al. The relation of diet, cigarette smoking, and alcohol consumption to plasma beta- carotene and alpha tocopherol levels. Am. J. Epidemiology 1988: 127, 283–96.

    CAS  Google Scholar 

  31. Riemersma, R. A., Wood, D. A., MacIntyre, C. C. A.et al. Risk of angina pectoris and plasma concentrations of vitamins A, C and E and carotene. Lancet 1991: 337, 1–5.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiology, The Adelaide Hospital, Dublin

    R. Clarke & I. Graham

  2. National Screening Centre for Metabolic Diseases, The Children’s Hospital, Temple Street, Dublin

    R. Clarke

  3. The Adelaide Hospital, and the National Screening Centre for Metabolic Diseases, The Children’s Hospital, Temple Street, Dublin

    E. Naughten & S. Cahalane

  4. The Department of Nutrition, The College of Technology, Dublin

    K. O. Sullivan & P. Mathias

  5. Sir Patrick Duns Research Unit, Trinity College, Dublin

    T. McCall

Authors
  1. R. Clarke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. Naughten
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Cahalane
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. O. Sullivan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Mathias
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T. McCall
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. I. Graham
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported in part by a grant from the Health Research Board of Ireland.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Clarke, R., Naughten, E., Cahalane, S. et al. The Role of Free Radicals as Mediators of Endothelial Cell Injury in Hyperhomocysteinemia. I.J.M.S. 161, 561–564 (1992). https://doi.org/10.1007/BF02940559

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02940559

Keywords

Search

Navigation