Abstract
Background: Oxidized lipoproteins may play an important role in the pathogenesis of atherosclerosis, and it has been shown that antioxidants have a protective effect against the progression of atherosclerosis.
Hypothesis: The aim of this study was to investigate the oxidative susceptibility of apolipoprotein B‐containing lipoproteins and antioxidant status in patients with acute coronary syndromes and chronic stable angina pectoris.
Methods: The study population included 70 patients with acute coronary syndromes (14 with recent acute myocardial infarction and 56 with unstable angina pectoris), 105 patients with stable angina pectoris, and 75 control subjects. In addition to conventional lipid and lipoprotein analysis, the susceptibility of apolipoprotein B‐containing lipoproteins to in vitro oxidation (lag phase) and plasma vitamin E and total carotene levels was measured.
Results: The lag phase was significantly shorter in patients with acute coronary syndromes (45 ± 12 min) than in patients with stable angina pectoris (51 ± 10 min) and in control subjects (58 ± 9 min) (p < 0.0001). Both plasma vitamin E and total carotene levels were lowest in patients with acute coronary syndromes (1.11 ± 0.32 mg/dl and 119 ± 32 μg/dl, respectively), followed by patients with stable angina pectoris (1.25 ± 0.37 mg/dl and 132 ± 37 μg/dl) and then controls (1.52 ± 0.31 mg/dl and 167 ± 41 μg/dl).
Conclusions: These data suggest that there is an intense oxidative process and a lower antioxidant status in acute coronary syndromes. This may lead to plaque instability due to the activation of the inflammatory response in coronary atherosclerotic lesions.
Keywords: lipoprotein oxidation, antioxidants, acute coronary syndromes, stable coronary artery disease
Full Text
The Full Text of this article is available as a PDF (400.6 KB).
References
- 1. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL: Beyond cholesterol: Modifications of low density lipoprotein that increase its atherogenecity. N Engl J Med 1989; 320: 915–924 [DOI] [PubMed] [Google Scholar]
- 2. Witztum JL, Steinberg D: Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest 1991; 88: 1785–1792 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Jialal I, Grundy SM: Influence of antioxidant vitamins on LDL oxidation. Ann N Y Acad Sci 1992; 669: 2327–2348 [DOI] [PubMed] [Google Scholar]
- 4. Brown MS, Goldstein JL: Lipoprotein metabolism in the macrophage: Implications for cholesterol deposition in atherosclerosis. Ann Rev Biochem 1983; 52: 223–261 [DOI] [PubMed] [Google Scholar]
- 5. Cathcort MK, Morel DW, Chisholm GM: Monocytes and neutrophils oxidize low density lipoprotein making it cytotoxic. J Leucocyt Biol 1985; 38: 341–350 [DOI] [PubMed] [Google Scholar]
- 6. Quinn MT, Parthasarathy S, Fong LG, Steinberg D: Oxidatively modified low density lipoproteins: A potential role in recruitment and retention of monocyte/macrophages during atherogenesis. Practical Acad Sci USA 1987; 84: 2995–2998 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Esterbauer H, Gebicki J, Puhl H, Jurgens G: The role of lipid peroxidation and antioxidants in the oxidative modification of LDL. Free Radic Biol Med 1992; 13: 341–390 [DOI] [PubMed] [Google Scholar]
- 8. Nilsson J: Lipid oxidation, vascular inflammation and coronary atherosclerosis. Transplant Proc 1993; 25: 2063–2064 [PubMed] [Google Scholar]
- 9. Esterbauer H, Dieber‐Rotheneder M, Waeg G, Puhl H, Tatzber F: Endogenous antioxidants and lipoprotein oxidation. Biochem Soc Trans 1990; 18: 1059–1061 [DOI] [PubMed] [Google Scholar]
- 10. Gey KF, Puska P: Plasma vitamin E and A inversely related to mortality from ischemic heart disease in cross‐cultural epidemiology. Ann NY Acad Sci 1989; 570: 268–282 [DOI] [PubMed] [Google Scholar]
- 11. Gey KF, Puska P, Jordan P, Moser U: Inverse correlation between vitamin E and mortality from ischemic heart disease in cross‐cultural epidemiology. Am J Clin Nutr 1992; 53: 326–331 [DOI] [PubMed] [Google Scholar]
- 12. Demacker PNM, Vos‐Janssen HE, Hijmans AGM, van't Laar A, Jansen AP: Measurement of high density lipoprotein cholesterol in serum. Comparison of six isolation methods with enzymatic cholesterol analysis. Clin Chem 1980; 26 (13): 1780–1786 [PubMed] [Google Scholar]
- 13. Friedewald WT, Levy RI, Fredricksen DS: Estimation of the concentration of low‐density lipoprotein cholesterol in plasma, without use of preparative ultracentrifuge. Clin Chem 1972; 18 (6): 499–502 [PubMed] [Google Scholar]
- 14. Varley H: Vitamins In Practical Clinical Biochemistry, Hormones, Vitamins, Drugs and Poisons, (Eds. Varley H, Gowenlock AH, Bell M.), p. 222–223. London: William Heinemann Medical Books Ltd., 1976. [Google Scholar]
- 15. Neeld JB, Pearson WN: Macro and micromethods for the determination of serum vitamin A using trifluoroacetic acid. J Nutr 1963; 79: 454–462 [DOI] [PubMed] [Google Scholar]
- 16. Jialal I, Deveraj S: Low density lipoprotein oxidation, antioxidants, and atherosclerosis: A clinical biochemistry perspective. Clin Chem 1996; 42 (4): 498–506 [PubMed] [Google Scholar]
- 17. Zhang A, Vertommen J, Gaal LV, Leeuw D: A rapid and simple method for measuring the susceptibility of low‐density‐lipoprotein to copper‐catalyzed oxidation. Clin Chem Acta 2994; 227: 159–173 [DOI] [PubMed] [Google Scholar]
- 18. Gensini GG: A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol 1983; 51: 606–616 [DOI] [PubMed] [Google Scholar]
- 19. Thomas CE, Jackson RL, Ohlweiler DF, Ku J: Multiple lipid oxidation products in LDL induce interleukin‐lb release from human blood mononuclear cells. J Lipid Res 1994; 35: 417–427 [PubMed] [Google Scholar]
- 20. Clinton SK, Libby P: Cytokines and growth factors in atherogenesis. Arch Path Lab Med 1992; 116: 1292–1300 [PubMed] [Google Scholar]
- 21. Steinberg D: Low density lipoprotein oxidation and its pathobio‐logical significance. J Biol Chem 1997; 272: 20963–20966 [DOI] [PubMed] [Google Scholar]
- 22. Berliner JA, Heinecke JW: The role of oxidized lipoproteins in atherogenesis. Free Radic Biol Med 1996; 20: 707–727 [DOI] [PubMed] [Google Scholar]
- 23. Kostner K, Hornykewycz S, Yang P: Is oxidative stress causally linked to unstable angina pectoris? A study in 100 CAD patients and matched controls. Cardiovasc Res 1997; 36: 330–336 [DOI] [PubMed] [Google Scholar]
- 24. Holvoet P, Vanhaecke J, Janssens S, Van de Werf F, Collen D: Oxidized LDL and malondialdehyde‐modified LDL in patients with acute coronary syndromes and stable coronary artery disease. Circulation 1998; 98: 1487–1494 [DOI] [PubMed] [Google Scholar]
- 25. Regnström J, Nilsson J, Tornvall P, Landou C, Hamsten A: Susceptibility to low density lipoprotein oxidation and coronary atherosclerosis in man. Lancet 1992; 339: 1183–1186 [DOI] [PubMed] [Google Scholar]
- 26. Devaraj S, Jialal I: Oxidized low density lipoprotein and atherosclerosis. Int J Clin Lab Res 1996; 26: 178–184 [DOI] [PubMed] [Google Scholar]
- 27. Jialal I: Micronutrient modulation of nonconventional risk factors for coronary artery disease: LDL oxidation and hyperhomocys‐teinemia. Postgrad Med 1997; 41: 13–20 [Google Scholar]
- 28. Stephens SG, Parsons A, Schofield PM, Kelly F, Cheesman K, Mitchinson MJ, Brown MJ: Randomized controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 1996; 347: 781–786 [DOI] [PubMed] [Google Scholar]