Antibody-Like Immunoglobulins G Against Low Density Lipoprotein that Stimulate LIPID Accumulation in Cultured Cells

  • Alexander N. Orekhov
  • Vladimir V. Tertov
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 285)


Recently, we have found that low density lipoprotein (LDL) derived from the blood of patients with angiographically documented coronary atherosclerosis has an atherogenic potential which manifests itself in cultures of human aortic intimal cells in the accumulation of cellular lipids (mostly free and esterified cholesterol), elevation of proliferative activity and stimulation of extracellular matrix synthesis.1–6 LDL of most healthy donors were devoid of such atherogenic potential. We have established that atherogenic LDL circulating in patients blood is modified lipoprotein differing from nonatherogenic LDL of healthy donors by a low sialic acid content.7 On the other hand, rpinnyai of immunoglobulins C (IgC) fraction from the whole serum of atherosclerotic patients substantially decreased its atherogenic potential.8 We have assumed that the blood serum of atherosclerotic patients contains autoantibodies against modified (desialylated) LDL since the antibodies against LDL can stimulate the accumulation of intracellular cholesterol.9,10


Immune Complex Healthy Donor Affinity Constant Cellular Cholesterol Circulate Immune Complex 
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  1. 1.
    A. N. Orekhov, V. V. Tertov, S. N. Pokrovsky, I. Yu. Adamova, 0. N. Martsenyuk, A. A. Lyakishev and V. N. Smirnov, Blood serum atherogenicity associated with coronary atherosclerosis. Evidence for nonlipid factor providing atherogenicity of low-density lipoproteins and an approach to its elimination, Circ. Res. 62:421 (1988).PubMedGoogle Scholar
  2. 2.
    V. V. Tertov, A. N. Orekhov, 0. N. Martsenyuk, N. V. Perova and V. N. Smirnov, Low density lipoproteins isolated from the blood of patients with coronary heart disease induce the accumulation of lipids in human aortic cells, Exp. Mol. Pathol. 50:337 (1989).PubMedCrossRefGoogle Scholar
  3. 3.
    V. V. Tertov, A. N. Orekhov, H. R. Li and V. N. Smirnov, Intra cellular cholesterol accumulation is accompanied by enhanced proliferative activity of human aortic intimal cells, TisjsueCell 20:849 (1988).Google Scholar
  4. 4.
    A. N. Orekhov, V. V. Tertov, S. A. Kudryashov and V. N. Smirnov, Triggerlike stimulation of cholesterol accumulation and DNA and extracellular matrix synthesis induced by atherogenic serum or low density lipoprotein in cultured cells, Circ. Res. 66:311 (1990).PubMedGoogle Scholar
  5. 5.
    E. I. Chazov, V. V. Tertov, A. N. Orekhov, A. A. Lyakishev, N. V. Perova, Kh. A. Kurdanov, Kh. A. Khashimov, I. D. Novikov and V. N. Smirnov, Atherogenicity of blood serum from patients with coronary heart disease, Lancet 2:595 (1986).PubMedCrossRefGoogle Scholar
  6. 6.
    E. I. Chazov, A. N. Orekhov, V. V. Tertov, S. N. Pokrovsky, I. Yu. Adamova, A. A. Lyakishev, N. A. Gratsianski, A. S. Nechaev, N. V. Perova, Kh. A. Khashimov, Kh. A. Kurdanov, V. V. Kukharchuk and V. N. Smirnov, Atherogenicity of blood plasma from patients with coronary atherosclerosis and its correction, Atherosclerosis Rev. 17:9 (1988).Google Scholar
  7. 7.
    A. N. Orekhov, V. V. Tertov, D. N. Mukhin and I. A. Mikhailenko, Modification of low density lipoprotein by desialylation causes lipid accumulation in cultured cells. Discovery of desialylated lipoprotein with altered cellular metabolism in the blood of atherosclerotic patients, Biochem. Bipphys. Res. Comomun. 162:206 (1989).CrossRefGoogle Scholar
  8. 8.
    V. V. Tertov, A. N. Orekhov, Kh. S. Sayadyan, S. G. Serebrennikov, A. G. Kacharava, A. A. Lyakishev and V. N. Smirnov, Correlation between cholesterol content in circulating immune complexes and atherogenic properties of CHD patients’ serum manifested in cell culture, Atherosclerosis 81:183 (1990).PubMedCrossRefGoogle Scholar
  9. 9.
    A. N. Klimov, A. D. Denisenko, A. G. Vinogradov, V. A. Nagornev, Y. I. Pivovarova, O. D. Sitnikova and V. M. Pleskov, Accumulation of cholesteryl esters in macrophages incubated with human-antibody auto immune comp1ex, Atherosclerosis 74:41 (1988).PubMedCrossRefGoogle Scholar
  10. 10.
    A. N. Orekhov, V. V. Tertov, D.N. Mukhin, V. E. Koteliansky, M. A. Glukhova, M. G. Frid, G. K. Sukhova, Kh. A. Khashimov and V.N. Smirnov, Insolubilization of low density lipoprotein induces cholesterol accumulation in cultured subendothelial cells of human aorta, Attherosclerosis 79:59 (1989).CrossRefGoogle Scholar
  11. 11.
    F. T. Lindgren, Preparative ultracentrifugal laboratory procedures and suggestions for lipoprotein analysis, in: “Analysis of Lipids and Lipoproteins,” E. G. Perkins, ed., American Oil Chemical Society, New York, p. 205 (1975).Google Scholar
  12. 12.
    A. N. Orekhov, V. V. Tertov, I. D. Novikov, A. V. Krushinsky, E. R. Andreeva, V. Z. Lankin and V. N. Smirnov, Lipids in cells of atherosclerotic and uninvolved human aorta. I. Lipid composition of aortic tissue and enzyme isolated and cultured cells, Exp. Mol. Pathol. 42:117 (1985).PubMedCrossRefGoogle Scholar
  13. 13.
    O. H. Lowry, N. J. Rosenbrough, A. L. Farr, R. J. Randall, Protein measurement with the Folin phenol reagent, J. Biol. Chem. 193:265 (1951).PubMedGoogle Scholar
  14. 14.
    A. Hara, N. S. Radin, Lipid extraction of tissue with a low-toxicity solvent, Anal. Biochem. 90:420 (1978).PubMedCrossRefGoogle Scholar
  15. 15.
    W. D. Creighton, P. H. Lambert and P.A. Misher, Detection of anti bodies and soluble antigen-antibody complexes by precipitation with polyethylene glycol, J. Immunol. 111:1219 (1973).PubMedGoogle Scholar
  16. 16.
    J. Brock, Immunoglobulin isolation, in: “Immunologische Arbei-tsmethoden,” H. Friemel, ed., VEB Gustav Fischer Verlag, Jena, p. 390 (1984).Google Scholar
  17. 17.
    R. Muller, Calculation of average antibody affinity in anti-hapten sera from data obtained by competitive radioimmunoassay, J. Immunol. Methods 34:345 (1980).PubMedCrossRefGoogle Scholar
  18. 18.
    W. J. Dixon and M. B. Brown, “Biomedical Computer Programs. P-Series,” University of California Press, Berkeley, p. 185 (1977).Google Scholar
  19. 19.
    J.-L. Beaumont, L’hyperlipidemie par auto-anticorps anti-beta-lipoproteine. Une nouvelle entite pathologique, C. R. Acad. Sci. Paris [Ser D] 261:4563 (1965).Google Scholar
  20. 20.
    J. S. Taylor, L. A. Lewis, J. D. Battle, Jr, A. Butkus, A. L. Robertson, S. Deodhar and H. H. Roenigk, Jr, Plane xanthoma and multiple myeloma with lipoprotein-paraprotein complexing, Arch. Dermatol. 114:425 (1978).PubMedCrossRefGoogle Scholar
  21. 21.
    P. J. Gallagher, B. D. Jones, C. R. Casey and G. P. Sharratt, Circulating immune complexes in cardiac disease, Atherosclerosis 44:241 (1982).PubMedCrossRefGoogle Scholar
  22. 22.
    E. Szondy, M. Horvath, Z. Mezey, J. Szekely, E. Lengyel, G. Fust and S. Gero, Free and complexed anti-lipoprotein antibodies in vascular diseases, Atherosclerosis 49:69 (1983).PubMedCrossRefGoogle Scholar
  23. 23.
    B. J. Bauer, K. Blashfield, D. A. Buthala and L. C. Ginsberg, Immunoglobulin as the major low density lipoprotein binding protein in plasma, Atherosclerosis 44:153 (1982).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Alexander N. Orekhov
    • 1
  • Vladimir V. Tertov
    • 1
  1. 1.Institute of Experimental CardiologyUSSR Cardiology Research CenterMoscowRussia

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