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. 1997 Apr;77(4):333–337. doi: 10.1136/hrt.77.4.333

Aspirin protects low density lipoprotein from oxidative modification.

K A Steer 1, T M Wallace 1, C H Bolton 1, M Hartog 1
PMCID: PMC484727  PMID: 9155612

Abstract

OBJECTIVE: To examine the effects of aspirin on the potential for oxidative modification of low density lipoprotein (LDL). DESIGN: Before and after trial. SETTING: University department of medicine within a district general hospital campus. PATIENTS: Ten healthy normolipidaemic volunteers drawn from laboratory and medical staff. INTERVENTIONS: Aspirin (enteric coated) 300 mg daily for two weeks. MAIN OUTCOME MEASURES: In vitro oxidation of LDL following ultraviolet C (UVC) irradiation with measurements made of malondialdehyde, conjugated dienes, and electrophoretic mobility. RESULTS: There was a significant decrease in malondialdehyde production from LDL modified by aspirin in vivo following exposure to UVC irradiation for 90 minutes, culminating in a 30% decrease by 240 minutes (mean (SD) 64.2 (9.12) v 89.6 (11.6) nmol/mg LDL protein, P = 0.029). These observations were borne out using LDL modified by aspirin in vitro. The UVC induced increase in relative electrophoretic mobility of LDL was also significantly reduced following aspirin treatment (mean (SD) 2.17 (0.16) v 2.66 (0.24), P = 0.012). CONCLUSIONS: Aspirin, both in vivo and in vitro, protects LDL against subsequent oxidative modification, providing an additional mechanism whereby aspirin may protect against atherosclerosis.

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Selected References

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  1. Arnaud J., Fortis I., Blachier S., Kia D., Favier A. Simultaneous determination of retinol, alpha-tocopherol and beta-carotene in serum by isocratic high-performance liquid chromatography. J Chromatogr. 1991 Dec 6;572(1-2):103–116. doi: 10.1016/0378-4347(91)80476-s. [DOI] [PubMed] [Google Scholar]
  2. Basu S. K., Goldstein J. L., Anderson G. W., Brown M. S. Degradation of cationized low density lipoprotein and regulation of cholesterol metabolism in homozygous familial hypercholesterolemia fibroblasts. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3178–3182. doi: 10.1073/pnas.73.9.3178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brown M. S., Goldstein J. L. Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. Annu Rev Biochem. 1983;52:223–261. doi: 10.1146/annurev.bi.52.070183.001255. [DOI] [PubMed] [Google Scholar]
  4. De Furia F. G., Cerami A., Bunn H. F., Lu Y. S., Peterson C. M. The effect of aspirin on sickling and oxygen affinity of erythrocytes. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3707–3710. doi: 10.1073/pnas.70.12.3707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Esterbauer H., Dieber-Rotheneder M., Waeg G., Striegl G., Jürgens G. Biochemical, structural, and functional properties of oxidized low-density lipoprotein. Chem Res Toxicol. 1990 Mar-Apr;3(2):77–92. doi: 10.1021/tx00014a001. [DOI] [PubMed] [Google Scholar]
  6. Fogelman A. M., Shechter I., Seager J., Hokom M., Child J. S., Edwards P. A. Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in human monocyte-macrophages. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2214–2218. doi: 10.1073/pnas.77.4.2214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Goldstein J. L., Ho Y. K., Basu S. K., Brown M. S. Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc Natl Acad Sci U S A. 1979 Jan;76(1):333–337. doi: 10.1073/pnas.76.1.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Grootveld M., Halliwell B. Aromatic hydroxylation as a potential measure of hydroxyl-radical formation in vivo. Identification of hydroxylated derivatives of salicylate in human body fluids. Biochem J. 1986 Jul 15;237(2):499–504. doi: 10.1042/bj2370499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hawkins D., Pinckard R. N., Crawford I. P., Farr R. S. Structural changes in human serum albumin induced by ingestion of acetylsalicylic acid. J Clin Invest. 1969 Mar;48(3):536–542. doi: 10.1172/JCI106011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hawkins D., Pinckard R. N., Crawford I. P., Farr R. S. Structural changes in human serum albumin induced by ingestion of acetylsalicylic acid. J Clin Invest. 1969 Mar;48(3):536–542. doi: 10.1172/JCI106011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Henriksen T., Mahoney E. M., Steinberg D. Enhanced macrophage degradation of low density lipoprotein previously incubated with cultured endothelial cells: recognition by receptors for acetylated low density lipoproteins. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6499–6503. doi: 10.1073/pnas.78.10.6499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hessler J. R., Robertson A. L., Jr, Chisolm G. M., 3rd LDL-induced cytotoxicity and its inhibition by HDL in human vascular smooth muscle and endothelial cells in culture. Atherosclerosis. 1979 Mar;32(3):213–229. doi: 10.1016/0021-9150(79)90166-7. [DOI] [PubMed] [Google Scholar]
  13. Iversen S. A., Cawood P., Dormandy T. L. A method for the measurement of a diene-conjugated derivative of linoleic acid, 18:2(9,11), in serum phospholipid, and possible origins. Ann Clin Biochem. 1985 Mar;22(Pt 2):137–140. doi: 10.1177/000456328502200204. [DOI] [PubMed] [Google Scholar]
  14. Jürgens G., Hoff H. F., Chisolm G. M., 3rd, Esterbauer H. Modification of human serum low density lipoprotein by oxidation--characterization and pathophysiological implications. Chem Phys Lipids. 1987 Nov-Dec;45(2-4):315–336. doi: 10.1016/0009-3084(87)90070-3. [DOI] [PubMed] [Google Scholar]
  15. Kirkova M., Ivancheva E., Russanov E. In vitro effects of aspirin on malondialdehyde formation and on activity of antioxidant and some metal-containing enzymes. Comp Biochem Physiol Pharmacol Toxicol Endocrinol. 1994 Jul;108(2):145–152. doi: 10.1016/1367-8280(94)90025-6. [DOI] [PubMed] [Google Scholar]
  16. Kleinveld H. A., Hak-Lemmers H. L., Stalenhoef A. F., Demacker P. N. Improved measurement of low-density-lipoprotein susceptibility to copper-induced oxidation: application of a short procedure for isolating low-density lipoprotein. Clin Chem. 1992 Oct;38(10):2066–2072. [PubMed] [Google Scholar]
  17. Kukreja R. C., Kontos H. A., Hess M. L., Ellis E. F. PGH synthase and lipoxygenase generate superoxide in the presence of NADH or NADPH. Circ Res. 1986 Dec;59(6):612–619. doi: 10.1161/01.res.59.6.612. [DOI] [PubMed] [Google Scholar]
  18. Mahley R. W., Innerarity T. L., Weisgraber K. B., Oh S. Y. Altered metabolism (in vivo and in vitro) of plasma lipoproteins after selective chemical modification of lysine residues of the apoproteins. J Clin Invest. 1979 Sep;64(3):743–750. doi: 10.1172/JCI109518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Manjula T. S., Devi C. S. Effect of aspirin on mitochondrial lipids in experimental myocardial infarction in rats. Biochem Mol Biol Int. 1993 Apr;29(5):921–928. [PubMed] [Google Scholar]
  20. Mazière C., Goldstein S., Moreau M., Mazière J. C., Polonovski J. Aspirin induces alterations in low-density lipoprotein and decreases its catabolism by cultured human fibroblasts. FEBS Lett. 1987 Jun 29;218(2):243–246. doi: 10.1016/0014-5793(87)81054-2. [DOI] [PubMed] [Google Scholar]
  21. PIPER J., ORRILD L. Essential familial hypercholesterolemia and xanthomatosis; follow-up study of twelve Danish families. Am J Med. 1956 Jul;21(1):34–46. doi: 10.1016/0002-9343(56)90006-7. [DOI] [PubMed] [Google Scholar]
  22. Parthasarathy S., Khoo J. C., Miller E., Barnett J., Witztum J. L., Steinberg D. Low density lipoprotein rich in oleic acid is protected against oxidative modification: implications for dietary prevention of atherosclerosis. Proc Natl Acad Sci U S A. 1990 May;87(10):3894–3898. doi: 10.1073/pnas.87.10.3894. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pihan G., Regillo C., Szabo S. Free radicals and lipid peroxidation in ethanol- or aspirin-induced gastric mucosal injury. Dig Dis Sci. 1987 Dec;32(12):1395–1401. doi: 10.1007/BF01296666. [DOI] [PubMed] [Google Scholar]
  24. Pinckard R. N., Hawkins D., Farr R. S. In vitro acetylation of plasma proteins, enzymes and DNA by aspirin. Nature. 1968 Jul 6;219(5149):68–69. doi: 10.1038/219068a0. [DOI] [PubMed] [Google Scholar]
  25. Quinn M. T., Parthasarathy S., Fong L. G., Steinberg D. Oxidatively modified low density lipoproteins: a potential role in recruitment and retention of monocyte/macrophages during atherogenesis. Proc Natl Acad Sci U S A. 1987 May;84(9):2995–2998. doi: 10.1073/pnas.84.9.2995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Quinn M. T., Parthasarathy S., Steinberg D. Endothelial cell-derived chemotactic activity for mouse peritoneal macrophages and the effects of modified forms of low density lipoprotein. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5949–5953. doi: 10.1073/pnas.82.17.5949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Riley M. L., Harding J. J. The reaction of malondialdehyde with lens proteins and the protective effect of aspirin. Biochim Biophys Acta. 1993 Oct 3;1158(2):107–112. doi: 10.1016/0304-4165(93)90003-q. [DOI] [PubMed] [Google Scholar]
  28. Schwarz K. B., Arey B. J., Tolman K., Mahanty S. Iron chelation as a possible mechanism for aspirin-induced malondialdehyde production by mouse liver microsomes and mitochondria. J Clin Invest. 1988 Jan;81(1):165–170. doi: 10.1172/JCI113289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Shepherd J., Cobbe S. M., Ford I., Isles C. G., Lorimer A. R., MacFarlane P. W., McKillop J. H., Packard C. J. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995 Nov 16;333(20):1301–1307. doi: 10.1056/NEJM199511163332001. [DOI] [PubMed] [Google Scholar]
  30. Steinberg D., Parthasarathy S., Carew T. E., Khoo J. C., Witztum J. L. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989 Apr 6;320(14):915–924. doi: 10.1056/NEJM198904063201407. [DOI] [PubMed] [Google Scholar]
  31. Young I. S., Trimble E. R. Measurement of malondialdehyde in plasma by high performance liquid chromatography with fluorimetric detection. Ann Clin Biochem. 1991 Sep;28(Pt 5):504–508. doi: 10.1177/000456329102800514. [DOI] [PubMed] [Google Scholar]

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