Skip to main content
Log in

Role of oxidized human plasma low density lipoproteins in atherosclerosis: effects on smooth muscle cell proliferation

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

Abstract

The effects of oxidized human plasma low density lipoproteins (Ox-LDL) on the proliferation of cultured aortic smooth muscle cells was studied, employing viable cell counting, [3H] thymidine incorporation into DNA, and the release of lactate dehydrogenase (LDH) into the medium. Oxidized LDL (prepared by incubation of LDL with copper sulfate) exerted a concentration-dependent stimulation (2 fold, compared to control) of aortic smooth muscle cell proliferation at low concentrations (0.1 µg – 10 µg/ml medium). On the other hand, at high concentrations (25–200 µg/ml), Ox-LDL produced a pronounced decrease in viable cells, a decrease in the incorporation of [3H] thymidine into DNA, and an increase in the release of LDH in the medium. In this report, the previously postulated biological roles of oxidized-LDL in atherosclerosis are discussed in view of these findings.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

Ox-LDL:

Oxidized human plasma Low Density Lipoproteins

SMC:

Smooth Muscle Cells

LDH:

Lactate Dehydrogenase

LPC:

Lysophosphatidycholine

PC:

Phosphatidylcholine

TNF:

Tumor Necrosis Factor

References

  1. Goldstein JL, Brown MS: In: Schriver et al. (eds) The Metabolic Basis of Inherited Disease. McGraw-Hill, New York, Vol. 1, 1989, pp 1215–1250

    Google Scholar 

  2. Parathsarathy S, Quinn MT, Schwenke DC, Carew TE, Steinberg D: Oxidative modification of Beta-Very Low Density Lipoproteins: Potential role in monocyte recruitment and foam cell formation. Atherosclerosis 9: 398–404, 1989

    Google Scholar 

  3. Tertov VV, Kacharawa AG, Martsenyuk ON, Mukhin DN, Rogova EM, Orekov AN: Low density lipoproteins isolated from blood of coronary patients cause lipid accumulation in human aortic intimal cells. Path Physiol Gen Physiol 134–136, 1990

  4. Ross R: The smooth muscle cell: Growth of smooth muscle in culture and formation of elastic fibers. J Cell Biol 50: 172–186, 1971

    Google Scholar 

  5. Havel RJ, Eder HA, Bragdon JH: The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest 34: 1345–1353, 1955

    Google Scholar 

  6. Fogelman AM, Shechter I, Seager J, Hokom M, Childs JS, Edwards PA: Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in human monocyte macrophages. Proc Natl Acad Sci USA 77: 2214–2218, 1980

    Google Scholar 

  7. Chatterjee S: Gentamicin induced alterations in phospholipid metabolism in cultured human proximal tubular cells. J Biochem Toxicol 2: 181–201, 1987

    Google Scholar 

  8. Bartlett GR: Phosphorus assay in column chromatography. J Biol Chem 234: 466–468, 1959

    Google Scholar 

  9. Patterson MK Jr: In: WB Jakoby, IH Pastan (eds) Methods in Enzymol. LVIII. Academic Press, New York, 1979, pp 141–152

    Google Scholar 

  10. Chatterjee S, Sekerke CS, Kwiterovich PO: Effects of tunicamycin on the cell-surface binding, internalization and degradation of low density lipoproteins in human fibroblasts. Eur J Biochem 120: 435–441, 1981

    Google Scholar 

  11. Bergmeyer HU: In: Principles of Enzymatic analysis. Verlag Chemie, New York, 1978

    Google Scholar 

  12. Steinbrecher UP, Lougheed M, Kwon WC, Dinks M: Recognition of oxidized low density lipoproteins by the scavenger receptor of macrophages results from derivatization of apolipoprotein B by products of fatty acid peroxidation. J Biol Chem 264: 15216–15223, 1989

    Google Scholar 

  13. Henriksen T, Evensen SA, Urlander B: Injury to human endothelial cells in culture induced by low density lipoproteins. Scand J Clin Lab Invest 39: 361–368, 1979

    Google Scholar 

  14. Rajavashisth TB, Andalilei A, Territo MC, Berliner JA, Navab M, Fogelman AM, Lusis AJ: Induction of endothelial cell expression of granulocyte and macrophage colony stimulating factors by modified low density lipoproteins. Nature 344: 214–257, 1990

    Google Scholar 

  15. Sushing SD, Berliner JA, Valente AJ, Territo MC, Navab M, Parhami F, Gerritz R, Schwart CJ, Fogelman AM: Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells. Proc Natl Acad Sci USA 87: 5134–5138, 1990

    Google Scholar 

  16. Steinbrecher UP, Parathasarathy S, Leake PS, Witzum JL, Steinberg D: Modification of low density lipoproteins by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci USA 81: 3883–3887, 1974

    Google Scholar 

  17. Hessler JR, Robertson AL, Chisholm GM: Low density lipoprotein cytotoxicity induced by free radical peroxidation of lipid. J Lipid Res 24: 1070–1076, 1983

    Google Scholar 

  18. Quinn MT, Parathasarathy S, Steinberg D: Endothelial cell derived chemotactic activity for mouse peritoneal macrophages and the effects of modified forms of low density lipoproteins. Proc Natl Acad Sci USA 82: 5949–5953, 1985

    Google Scholar 

  19. Quinn MT, Parathasarathy S, Fogelman AM, Steinberg D: Oxidatively modified low density lipoproteins: A potential role in recruitment and retention of monocyte/macrophages during atherogenesis. Proc Natl Acad Sci USA 84: 2995–2998, 1987

    Google Scholar 

  20. Quinn MT, Parathasarathy S, Steinberg D: Lysosphosphatidylcholine: A chemotactic factor for human monocytes and its potential role in atberogenesis. Proc Natl Acad Sci USA 85: 2805–2809, 1985

    Google Scholar 

  21. Henriksen T, Mahoney EM, Steinberg D: Enhanced macrophage degradation of biologically modified low density lipoproteins. Arteriosclerosis 3: 149–159, 1983

    Google Scholar 

  22. Heinecke JW, Rosen H, Chait A: Iron and copper promote modification of low density lipoprotein by human arterial smooth muscle cells in culture. J Clin Invest 74: 1890–1894, 1984

    Google Scholar 

  23. Parathasarathy S, Printz DJ, Boyd D, Joy L, Steinberg D: Macrophage oxidation of low density lipoprotein generates a modified form recognized by the scavenger receptor. Arteriosclerosis 6: 505–510, 1986

    Google Scholar 

  24. Brown MS, Goldstein JL: Lipoprotein metabolism in the macrophage: Implications for cholesterol deposition in atherosclerosis. Annu Rev Biochem 52: 223–261, 1983

    Google Scholar 

  25. Quinn MT, Parathasarathy S, Steinberg D: Endothelial cellderived chemotactic activity for mouse peritoneal macrophages and the effects of modified forms of low density lipoprotein. Proc Natl Acad Sci USA 82: 5949–5953, 1989

    Google Scholar 

  26. Yokoyama M, Hirata KI, Miyahe R, Akita H, Ishikawa Y, Fukuaki H: Lysophosphatidylcholine: Essential role in the inhibition of endothelium-dependent vasorelaxation by oxidized low density lipoproteins. 168: 301–308, 1990

  27. Morton RE, West GA, Hoff HFL: A low density lipoproteinsized particle isolated from human atherosclerotic lesions is internalized by macrophages via a non-scavenger receptor mechanism. J Lipid Res 27: 1124–1134, 1986

    Google Scholar 

  28. Haberland ME, Fong D, Cheng L: Malondialdehyde-altered protein occurs in atheroma of Watanabe Heritable Hyperlipidemic rabbits. Science 241: 215, 1988

    Google Scholar 

  29. Carew TE, Schwenke DC, Steinberg D: Antiatherogenic effect of probucol unrelated to its hypocholesterolemic effect: Evidence that antioxidants in vivo can selectively inhibit low density lipoprotein degradation in macrophage rich fatty streaks and slow the progression of atherosclerosis in the Watanabe Heritable Hyperlipidemic rabbit. Proc Natl Acad Sci USA 84: 7725–7729, 1987

    Google Scholar 

  30. Kita T, Nagano Y, Yokode M, Ishii K, Kume N, Ooshimi A, Yoshida H, Kawai C: Probucol prevents the progression of atherosclerosis in Watanabe Heritable Hyperlipidemic rabbit, man animal model for familial hypercholesterolemia. Proc Natl Acad Sci USA 84: 5928–5931.

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chatterjee, S. Role of oxidized human plasma low density lipoproteins in atherosclerosis: effects on smooth muscle cell proliferation. Mol Cell Biochem 111, 143–147 (1992). https://doi.org/10.1007/BF00229586

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00229586

Key words

Navigation