Effect of Lipoproteins and Platelets on Macrophage Cholesterol Metabolism

  • Michael Aviram
Part of the Blood Cell Biochemistry book series (BLBI, volume 2)


Atherosclerosis is a complicated process that starts with cholesterol accumulation in the cells of the arterial wall, mainly in monocyte-derived macrophages. Later events in atherogenesis include the involvement of endothelial cells (EC), smooth muscle cells (SMC), platelets, and plasma lipoproteins. These events finally lead to the formation of fibrous plaque and complicated lesions.


Cholesteryl Ester Scavenger Receptor Mouse Peritoneal Macrophage Cholesterol Accumulation Chylomicron Remnant 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Aviram, M., 1987, Platelet modified low density lipoproteins: Studies in normal subjects and in patients with homozygous familial hypercholesterolemia, Clin. Biochem. 20: 91–95.PubMedGoogle Scholar
  2. Aviram, M., 1989a, Platelet secretory products enhances LDL receptor activity and inhibits scavenger receptor activity in human monocyte derived macrophages, Metabolism 38: 425–430.PubMedGoogle Scholar
  3. Aviram, M., 1989b, Low density lipoprotein and scavenger receptor activities are modulated by secretory products derived from cells of the arterial wall, Metabolism 38: 445–449.PubMedGoogle Scholar
  4. Aviram, M., and Brook, J. G., 1982, The effect of human plasma on platelet function in familial hypercholesterolemia. Thromb. Res. 26: 101–109.PubMedGoogle Scholar
  5. Aviram, M., and Brook, J. G., 1985, Abnormal plasma lipoprotein pattern and decreased platelet function in type V hyperlipoproteinemia, Isr. J. Med. Sci. 21: 898–904.PubMedGoogle Scholar
  6. Aviram, M., and Brook, J. G., 1987, Platelet activation by plasma lipoproteins, Prog. Card. Dis. 30: 61–72.Google Scholar
  7. Aviram, M., and Chait, A., 1988, Apolipoprotein E inhibits the uptake of acetylated LDL by the scavenger receptor on macrophages, Arteriosclerosis 8: 555a.Google Scholar
  8. Aviram, M., and Deckelbaum, R. J., 1989, Intralipid infusion into humans reduces in vitro platelet aggregation and alters platelet lipid composition, Metabolism 38: 343–347.PubMedGoogle Scholar
  9. Aviram, M., Fuhrman, B., Bulus, M., Ginsburg, H., and Brook, J. G., 1987, The effect of plasma lipoproteins on cholesterol accumulation in macrophages. Comparison between lipoproteins from normals and homozygous familial hypercholesterolemia, Atherosclerosis 65: 207–214.PubMedGoogle Scholar
  10. Aviram, M., Williams, K. J., Tall, A., Carpenter, Y., and Deckelbaum, R. J., 1989a, Intralipid infusion abolishes the ability of human serum to cholesterol load cultured macrophages, Arteriosclerosis 9: 67–75.PubMedGoogle Scholar
  11. Aviram, M., Bierman, E. L., and Chait, A., 1988a, Modification of low density lipoprotein by lipoprotein lipase or hepatic lipase induces enhanced uptake and cholesterol accumulation in cells, J. Biol. Chem. 263: 15416–15422.PubMedGoogle Scholar
  12. Aviram, M., Lund-Katz, S., Phillips, M., and Chait, A., 19886, The influence of the triglyceride content of low density lipoprotein on the interaction of apolipoprotein B-100 with cells, J. Biol. Chem. 263: 16842–16848.Google Scholar
  13. Aviram, M., Bierman, E. L., and Oram, J. F., 1989b, High density lipoprotein stimulates sterol translocation between intracellular and plasma membrane pools in human monocyte-derived macrophages, J. Lipid Res. 30: 65–76.PubMedGoogle Scholar
  14. Basu, S. K., Brown, M. S., Ho, Y. K., and Goldstein, J. L., 1979, Degradation of low density lipoproteindextran sulfate complexes associated with deposition of cholesteryl esters in mouse macrophages, J. Biol. Chem. 254: 7141–7146.PubMedGoogle Scholar
  15. Basu, S. K., Goldstein, J. L., and Brown, M. S., 1983, Independent pathways for secretion of cholesterol and apolipoprotein E by macrophages, Science 219: 871–873.Google Scholar
  16. Bernheimer, A. W., Robinson, W. G., Lindker, R., Mullins, D., Yup, Y. K., Cooper, N. S., Seidman, I., and Uwajima, T., 1987, Toxicity of enzymatically oxidized low density lipoprotein, Biochim. Biophys. Acta 148: 260–266.Google Scholar
  17. Borsum, T., Henriksen, T. W., and Reisvaag, M. 1983, Oxidized low density lipoprotein can reduce the pinocyte activity in cultured human endothelial cells as measured by cellular uptake of [14C]-sucrose, Atherosclerosis 58: 81–96.Google Scholar
  18. Bradley, W. A., Hwang, S. C., Karlin, J. B., Lin, A. H. Y., Prasad, S. C., Gotto, A. M., Gianturco, S. H., 1984, Low density lipoprotein receptor binding determinants switch from apolipoprotein E to apolipoprotein B during conversion of hypertriglyceridemic very low density lipoprotein to low density lipoproteins, J. Biol. Chem. 259: 14728–14735.Google Scholar
  19. Bradley, W. A., Song, J. N., and Gianturco, S. H., 1986, Thrombin/prothombin interactions with very low density lipoproteins, Ann. N.Y. Acad. Sci. 485: 159–169.PubMedGoogle Scholar
  20. Brown, M. S., and Goldstein, J. L., 1983. Lipoprotein metabolism in the macrophage, Annu. Rev. Biochem. 52: 223–261.PubMedGoogle Scholar
  21. Brown, M. S., and Goldstein, J. L., 1986, A receptor mediated pathway for cholesterol homeostasis, Science 232: 34–39.PubMedGoogle Scholar
  22. Brown, M. S., Goldstein, J. L., Krieger, M., Ho, Y. K., and Anderson, R. G. W., 1979, Reversible accumulation of cholesteryl ester in macrophages incubated with acetylated lipoproteins, J. Cell Biol. 82: 597–613.PubMedGoogle Scholar
  23. Brown, M. S., Basu, S. K., Falck, J. R., Ho, Y. K., and Goldstein, J. L., 1980a, The scavenger cell pathway for lipoprotein degradation: Specificity of the binding site that mediates the uptake of negatively-charging LDL by macrophages, J. Supramol. Struct. 13: 67–81.PubMedGoogle Scholar
  24. Brown, M. S., Ho, Y. K., and Goldstein, J. L., 1980b, The cholesteryl ester cycle in macrophage foam cells, J. Biol. Chem. 255: 9344–9352.PubMedGoogle Scholar
  25. Carew, T. E., Schwenke, D. C., and Steinberg, D., 1987, Antiatherogenic effect of probucol unrelated to its hypocholesterolemic effect: Evidence that antioxidants in vivo can selectively inhibit low density lipoprotein degradation in macrophages-rich fatty streaks and slow the progression of atherosclerosis in the Watanabe heritable hyperlipidemic (WHHL) rabbit, Proc. Natl. Acad. Sci. USA 84: 7725–7729.PubMedGoogle Scholar
  26. Chait, A., 1987, Progression of atherosclerosis: The cellular biology, Eur. Heart J. 8 (Suppl. E): 15–22.PubMedGoogle Scholar
  27. Chait, A., Eisenberg, S., Steinmetz, A., Albers, J. J. and Bierman, E. L., 1984, Low density lipoproteins modified by lipid transfer protein have altered biological activity, Biochim. Biophys. Acta 795: 314–325.PubMedGoogle Scholar
  28. Chandler, A. B., and Hand, R. A., 1961, Phagocytized platelets: A source of lipids in human thrombii and atherosclerotic plaques, Science 134: 946–947.PubMedGoogle Scholar
  29. Clevidence, B. A., Morton, R. E., West, G., Dusek, D. M., and Hoff, H. F., 1984, Cholesterol esterification in macrophages, Arteriosclerosis 4: 196–207.PubMedGoogle Scholar
  30. Curtiss, L. K., Black, A. S., Takagi, Y. and Plow, E. F., 1987, New mechanism for foam cell generation in atherosclerotic lesions, J. Clin. Invest. 80: 367–373.PubMedGoogle Scholar
  31. Daugherty, A., Zweylel, B. S., Sobel, B. E., and Schonfeld, G., 1987, Modified LDL in vascular tissue of WHHL rabbits, Arteriosclerosis 7: 527a.Google Scholar
  32. Eklund, A., Sjoblom, L., and Ostlund-Lindquist, A. M., 1986, Accumulation of cholesteryl ester and triglyceride in cullused macrophages incubated with plasma very low density lipoproteins from rats fed on casein or soybean protein diets containing moderate levels of cholesterol, Atherosclerosis 62: 129–136.PubMedGoogle Scholar
  33. Ellsworth, J. L., Cooper, A. D., and Kraemer, F. B., 1986, Evidence that chylomicron remnants and ß very low density lipoprotein are transported by the same receptor pathway in J774 murine macrophage-derived cells, J. Lipid Res. 27: 1062–1072.PubMedGoogle Scholar
  34. Ellsworth, J. L., Kraemer, F. B., and Cooper, A. D., 1987, Transport of ß very low density lipoproteins and chylomicron remnants by macrophages is mediated by the low density lipoprotein receptor pathway, J. Biol. Chem. 262: 2316–2325.PubMedGoogle Scholar
  35. Esterbauer, H., Jurgens, G., Quehenberger, O., and Koller, E., 1987, Autooxidation of human low density lipoprotein: Loss of polyunsaturated fatty acids and vitamin E and generation of aldehydes, J. Lipid Res. 28: 495–509.Google Scholar
  36. Fogelman, A. M., Shechter, I., Seager, J., Hokom, M., Child, J. S., and Edwards, P. A., 1980, Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in human monocyte-macrophages, Proc. Natl. Acad. Sci. USA 77: 2214–2218.PubMedGoogle Scholar
  37. Fogelman, A. M., Hokom, M. M., Haberland, M. E., Tanaka, R. D., and Edwards, P. A., 1982, Lipoprotein regulation of cholesterol metabolism in macrophages derived from human monocytes, J. Biol. Chem. 257: 14081–14086.PubMedGoogle Scholar
  38. Fong, L. C., Parthasarathy, S., Witztum, T. L., and Steinberg, D., 1987, Nonenzymotic oxidative cleavage of peptide bonds in apoprotein B-100, J. Lipid Res. 28: 1466–1477.PubMedGoogle Scholar
  39. Fontaine, R. N., and Fielding, C. J., 1985, Comparison of cholesterol transport in pulmonary, peritoneal and blood-derived macrophages from normo and hypercholesterolemic rabbits, J. Lipid Res. 26: 915–923.PubMedGoogle Scholar
  40. Fox, P. L., and DiCorleto, P. E., 1986, Modified low density lipoproteins suppress production of a platelet derived growth factor-like protein by cultured endothelial cells, Proc. Natl. Acad. Sci. USA 83: 4774–4778.PubMedGoogle Scholar
  41. Esterbauer, H., Rothenden, M., Striegal, G., Waeg, G., Ashy, A., Sattler, W., and Jurgens, G., 1984, Vitamin E and other lipophilic antioxidants protect LDL against oxidation, Fat Sci Technol. 91: 316–324.Google Scholar
  42. Fuster, V., 1981, Role of platelets in the development of atherosclerotic disease and possible interference with platelet inhibitor drugs, Scand. J. Haematol. 27: 1–34.Google Scholar
  43. Gerrity, R. G., 1981, The role of monocytes in atherogenesis, Am. J. Pathol. 103: 181–190.PubMedGoogle Scholar
  44. Gianturco, S. H., Bradley, W. A., Gotto, A. M., Morrisett, J. D., and Peary, D. L., 1982, Hypertriglyceridemia very low density lipoproteins induce triglyceride synthesis and accumulation in mouse peritoneal macrophages, J. Clin. Invest. 70: 168–178.PubMedGoogle Scholar
  45. Goldstein, J. L., and Brown, M. S., 1987, Regulation of low density lipoprotein receptors: Implications for pathogenesis and therapy of hypercholesterolemia and atherosclerosis, Circulation 76: 504–507.PubMedGoogle Scholar
  46. Goldstein, J. L., Hoff, H. F., Ho, Y. K., Basu, S. K., and Brown, M. S., 1981, Stimulation of cholesteryl ester synthesis in macrophages by extracts of atherosclerotic human aortas and complexes of albuminal cholesteryl esters, J. Lipid Res. 1: 40–226.Google Scholar
  47. Haberland, M. E., Fogelman, A. M., and Edwards, P. A., 1982, Specifity of receptor-mediated recognition of malondialdehyde-modified low density lipoproteins, Proc. Natl. Acad. Sci. USA 79: 1712–1716.PubMedGoogle Scholar
  48. Haberland, M. E., Olch, C. L., and Fogelman, A. M., 1984, Role of lysines in mediating interaction of modified low density lipoproteins with the scavenger receptor of human monocyte macrophages, J. Biol. Chem. 259: 11305–11311.PubMedGoogle Scholar
  49. Haberland, M. E., Fong, D., and Cheng, L., 1987, Malondialdehyde-altered apo B protein occurs in arterial lesions of Watanabe hereditable hyperlipidemic rabbits(WHHL) rabbits, Arteriosclerosis 7: 536a.Google Scholar
  50. Hartung, H. P., Kladelzky, R. G., Melnik, B., and Hennerici, M., 1986, Stimulation of the scavenger receptor on monocyte-macrophages evokes release of arachidemic acid metabolites and reduced oxygen species, Lab. Invest. 55: 209–216.PubMedGoogle Scholar
  51. Havel, R. J., 1985, Role of the liver in atherosclerosis, Arteriosclerosis 5: 569–580.PubMedGoogle Scholar
  52. Heinecke, J. W., 1987, Free radical modification of low density lipoproteins: Mechanisms and biological consequences, Free Radical Biol. Med. 3: 65–73.Google Scholar
  53. Heinecke, J. W., Rosen, H., Suzuki, L., and Chait, A., 1987, The role of sulfur-containing amino acids in superoxide production and modification of low density lipoprotein by arterial smooth muscle cells, J. Biol. Chem. 262: 10098–10103.PubMedGoogle Scholar
  54. Henricksen, T., Mahoney, E. M., and Steinberg, D., 1981. 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. USA 78: 6499–6503.Google Scholar
  55. Hessler, J. R., Morel, D. W., Lewis, L. J., and Chisholm, G. M., 1983, Lipoprotein oxidation and lipoprotein-induced cytotoxicity, Arteriosclerosis 3: 215–222.PubMedGoogle Scholar
  56. Ho, Y. K., Brown, M. S., and Goldstein, J. L., 1980, Hydrolysis and excretion of cytoplasmic cholesterol esters by macrophages: Stimulation by high density lipoprotein and other agents, J. Lipid Res. 21: 391–398.PubMedGoogle Scholar
  57. Hoff, H. F., Morel, D. W., Jurgens, G., Esterbauer, H., and Chisholm, G. M., 1987, Modification of LDL by 4-hydroxynonenal induces enhanced uptake by macrophages and cytotoxicity to proliferating fibroblasts, Arteriosclerosis 7: 523a.Google Scholar
  58. Innerarity, T. L., Pitas, R. E., and Mahley, R. W., 1982, Modulating effects of canine high density lipoproteins on cholesteryl ester synthesis induced by 3-very low density lipoproteins in macrophages, Arteriosclerosis 2: 114–124.PubMedGoogle Scholar
  59. Innerarity, T. L., Arnold, K. S., Weisgraber, K. H., and Mahley, R. W., 1986, Apolipoprotein E is the determinant that mediates the receptor uptake of 13 very low density lipoproteins by mouse macrophages, Arteriosclerosis 6: 114–122.PubMedGoogle Scholar
  60. Karlin, J. B., Johnson, W. J., Benedict, C. R., Chacko, G. K., Phillips, M. C., and Rothblat, G. H., 1987, Cholesterol flux between cells and high density lipoprotein, J. Biol. Chem. 262: 12557–12564.PubMedGoogle Scholar
  61. Khoo, J. C., Miller, E., McLoughlin, P., and Steinberg, D., 1988, Enhanced macrophage uptake of low density lipoprotein after self aggregation, Arteriosclerosis 8: 73–62.Google Scholar
  62. Kita, T., Yokode, M., Watanabe, Y., Narumiya, S., and Kawai, C., 1986, Stimulation of cholesteryl ester synthesis in mouse peritoneal macrophages by cholesterol-rich very low density lipoproteins from the Watanabe heritable hyperlipidemic rabbits, an animal model of familial hypercholesterolemia, J. Clin. Invest. 77: 1460–1465.PubMedGoogle Scholar
  63. Kita, T., Nagano, Y., Yokodi, M., Ishii, K., Kume, N., Oushima, A., Yoshida, H., and Kawai, C., 1987, Probucol prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits: An animal model for familial hypercholesterolemia, Proc. Natl. Acad. Sci. USA 84: 5928–5931.PubMedGoogle Scholar
  64. Kleinman, Y., Krul, E. S., Burne, S. M., Aronson, W., Pfleger, B., and Schonfeld, G., 1988, Lipolysis of LDL with phospholipase A2 alters the expression of selected apo B-100 epitopes and the interaction of LDL with cells, J. Lipid Res. 29: 729–743.PubMedGoogle Scholar
  65. Knight, B. L., Thompson, G. R., and Sontar, A. K., 1986, Binding and degradation of heavy and light subfractions of low density lipoprotein by cultured fibroblasts and macrophages, Atherosclerosis 59: 301–306.PubMedGoogle Scholar
  66. Knight, B. L., Soutar, A. K., and Patel, D. D., 1987, Nonsaturable degradation of LDL by monocyte-derived macrophages leads to a reduction of HMG CoA reductase activity with little synthesis of cholestryl esters, Atherosclerosis 64: 131–138.PubMedGoogle Scholar
  67. Kokkonen, J. O., and Kovanen, P. T., 1987, Stimulation of mast cells leads to cholesterol accumulation in macrophages in vitro by a mast cell granule-mediated uptake of low density lipoprotein, Proc. Natl. Acad. Sci. USA 84: 2287–2291.PubMedGoogle Scholar
  68. Koo, C., Wernette-Hammond, M. E., and Innerarity, T. L., 1986, Uptake of canine 0-very low density lipoproteins by mouse peritoneal macrophages is mediated by a low density lipoprotein receptor, J. Biol. Chem. 261: 11194–11201.PubMedGoogle Scholar
  69. Kraemer, F. B., Chen, Y. D., Lopez, R. D., and Reaven, G. M., 1983, Characterization of the binding site on thioglycolate stimulated mouse peritoneal macrophages that mediates the uptake of very low density lipoproteins, J. Biol. Chem. 258: 12190–12197.PubMedGoogle Scholar
  70. Krempler, F., Kostner, G. M., Roscher, A., Bolzano, K., and Sandhrofer, F., 1984, The interaction of human apo B-containing lipoproteins with mouse peritoneal macrophages: A comparison of Lp(a) with LDL, J. Lipid Res. 25: 283–287.PubMedGoogle Scholar
  71. Kruth, H. S., 1985, Platelet mediated cholesterol accumulation in cultured aortic smooth muscle cells, Science 227: 1243–1245.PubMedGoogle Scholar
  72. Lindqvist, P., Ostlund-Lindqvist, A. M., Witztum, J. L., Steinberg, D., and Little, J. A., 1983, The role of lipoprotein lipase in the metabolism of triglyceride-rich lipoproteins by macrophages, J. Biol. Chem. 258: 9086–9092.PubMedGoogle Scholar
  73. Mahley, R. W., 1985, Atherogenic lipoproteins and coronary artery disease, Circulation 72: 943–948.PubMedGoogle Scholar
  74. Mahley, R. W., and Innerarity, T. L., 1983, Lipoprotein receptors and cholesterol homeostasis, Biochim. Biophys. Acta 737: 197–203.PubMedGoogle Scholar
  75. Mahley, R. W., Innerarity, T. L., Brown, M. S., Ho, Y. K., Goldstein, J. L., 1980, cholesterol ester synthesis in macrophages: Stimulation by ß very low density lipoproteins from cholesterol-fed animals of several species, J. Lipid Res. 21: 970–980.Google Scholar
  76. Mazzone, T., Gump, H., Diller, P., and Getz, G. S., 1987, Macrophage free cholesterol content regulates apolipoprotein E synthesis, J. Biol. Chem. 962: 11657–11662.Google Scholar
  77. McCloskey, H. M., Rothblat, G. H., and Glick, J. M., 1987, Incubation of aceylated low density lipoprotein with cholesterol-rich dispersions enhances cholesterol uptake by macrophages, Biochim. Biophys. Acta 921: 320–332.PubMedGoogle Scholar
  78. Mendelsohn, M. E., and Loscalzo, J., 1988, Role of platelets in cholesteryl ester formation by U937 cells, J. Clin. Invest. 81: 62–68.PubMedGoogle Scholar
  79. Miller, G. J., and Miller, N. E., 1975, Plasma high density lipoprotein concentration and development of ischemic heart diseases, Lancet 1: 16–19.PubMedGoogle Scholar
  80. Mitchinson, M. J., and Ball, R. Y., 1987, Macrophages and atherosclerosis, Lancet 11: 146–149.Google Scholar
  81. Morel, D. W., Hessler, J. R., and Chisholm, G. M., 1983a, Low density lipoprotein cytotoxicity induced by free radical peroxidation of lipid, J. Lipid Res. 24: 1020–1076.Google Scholar
  82. Morel, D. W., Hessler, J. R., and Chisholm, G. M., 1983b, Low density lipoprotein cytotoxicity induced by free radical peroxidation of lipid, J. Lipid Res. 24: 1020–1076.Google Scholar
  83. Nagelkerke, J. F., Havekes, L., Van Hinsbergh, V. W. M., and Van Berkel, T. J. C., 1984, In vivo catabolism of biologically modified LDL, Arteriosclerosis 4: 256–264.PubMedGoogle Scholar
  84. Nathan, C. F., 1987, Secretory products of macrophages, J. Clin. Invest. 79: 319–326.PubMedGoogle Scholar
  85. Orekhov, A. N., Testov, V. V., Mukhin, D. N., Koteliansky, V. E., Khairulla, M. A., Khashimor, K. A., and Smirnov, V. N., 1987, Association of low density lipoprotein with particulate connective tissue matrix components enhances cholesterol accumulation in cultured subendothelial cells of human aorta, Biochim. Biophys. Acta 928: 251–258.PubMedGoogle Scholar
  86. Ostlund-Lindqvist, A. M., Gustafson, S., Lindqvist, P., Witztum, J. L., and Little, J. A., 1983, Uptake and degradation of human chylomicrons by macrophages in culture, Arteriosclerosis 3: 433–440.PubMedGoogle Scholar
  87. Owen, J. S., McIntyre, N., and Gillett, P. T., 1984, Lipoproteins, cell membranes and cellular functions, Trends Biochem. Sci. 6: 238–242.Google Scholar
  88. Parthasarathy, S., Printz, D. J., Boyd, R., Joy, L., and Steinberg, D., 1986a, Macrophage oxidation of low density lipoprotein generates a modified form recognized by the scavenger receptor, Arteriosclerosis 6: 505–510.PubMedGoogle Scholar
  89. Parthasarathy, S., Young, S. G., Witztum, J. L., Pittman, R. C., and Steinberg, D., 1986b, Probucol inhibits oxidative modification of low density lipoproteins, J. Clin. Invest. 77: 641–644.PubMedGoogle Scholar
  90. Parthasarathy, S., Forg, L., Otero, D., and Steinberg, D., 1987, Recognition of apoproteins from delipidated, oxidized, low density lipoprotein (LDL) by the acetyl-LDL receptor, Proc. Natl. Acad. Sci. USA 84: 537–540.PubMedGoogle Scholar
  91. Phillips, D. R., Arnold, K., and Innerarity, T. L., 1985, Platelet secretory products inhibit lipoprotein metabolism in macrophages, Nature (London) 316: 746–748.Google Scholar
  92. Pitas, R. E., Innerarity, T. L., and Mahley, R. W., 1983, Foam cells in explants of atherosclerotic rabbit aortas have receptors for ß very low density lipoproteins and modified low density lipoproteins, Arteriosclerosis 3: 2–12.PubMedGoogle Scholar
  93. Pittman, R. C., Knecht, T. P., Rosenbaum, M. S., and Taylor, C. A., 1987, A nonendocytotic mechanism for the selective uptake of high density lipoprotein-associated cholesterol esters, J. Biol. Chem. 262: 2443–2450.PubMedGoogle Scholar
  94. Polacek, D., Byrne, R. E., and Scanu, A. M., 1988, Modification of low density lipoproteins by polymorphonuclear cell elastase leads to enhanced uptake by human monocyte-derived macrophages via the low density lipoprotein receptor pathway, J. Lipid Res. 29: 797–808.PubMedGoogle Scholar
  95. Portman, O. W., O’Malley, J. P., and Alexander, M., 1987, Metabolism of native and acetylated low density lipoproteins in squirrel monkeys with emphasis on aorta with varying severities of atherosclerosis, Atherosclerosis 66: 227–235.PubMedGoogle Scholar
  96. Quinn, M. T., Parathasarathy, S., and Steinberg, D., 1985, Endothelial cell-derived chemotactic activity for mouse peritoneal macrophages and the effects of modified forms of low density lipoprotein, Proc. Natl. Acad. Sci. USA 82: 5949–5953.PubMedGoogle Scholar
  97. Quinn, M. T., Parathasarathy, S., Fong, L., and Steinberg, D., 1987, 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.PubMedGoogle Scholar
  98. Raymond, T. L., and Reynolds, S. A., 1983, Lipoproteins of the extravascular space: Alterations in low density lipoproteins of interstitial inflammatory fluid, J. Lipid Res. 24: 113–119.PubMedGoogle Scholar
  99. Raymond, T. L., Reynolds, S. A., and Swanson, J. A., 1987, In vitro incubation of low density lipoproteins with inflammatory cells causes enhanced degradation by macrophages in culture, Inflammation 11: 335–343.PubMedGoogle Scholar
  100. Ross, R., 1986, The pathogenesis of arteriosclerosis—an update, N. Engl. J. Med. 314: 488–500.PubMedGoogle Scholar
  101. Ross, R., 1987, Platelet derived growth factor, Annu. Rev. Med. 38: 71–79.PubMedGoogle Scholar
  102. Sacks, F. M., and Breslow, J. L., 1987, Very low density lipoproteins stimulate cholesteryl ester formation in U937 macrophages, Arteriosclerosis 7: 35–46.PubMedGoogle Scholar
  103. Salisbury, B. G., Falcone, D. J., and Minick, C. R., 1985, Insoluble low density lipoprotein-proteoglycan complexes enhance cholesteryl ester accumulation in macrophages, Am. J. Pathol. 120: 6–11.PubMedGoogle Scholar
  104. Salmon, S., Maziere, C., Theron, L., Beucler, I., Ayralt-Jarrier, M., Goldstein, S., and Polonovski, J., 1987, Immunological detection of low density lipoprotein modified by malondialdehyde in vitro or in vivo, Biochim Biophys. Acta 920: 215–220.PubMedGoogle Scholar
  105. Schmitz, E. S., Robenek, H., Lohmann, V., and Assmann, G., 1985, Interaction of high density lipoproteins with cholesteryl ester-laden macrophages: Biochemical and morphological characterization of cell surface receptor binding, endocytosis and resecretion of high density lipoproteins by macrophages, EMBO J. 4: 613–622.PubMedGoogle Scholar
  106. Schmitz, G., Assmann, G., Brennhausen, B., and Schaefer, H. J., 1987, Interaction of Tangier lipoproteins with cholesteryl ester-laden mouse peritoneal macrophages, J. Lipid Res. 28: 87–99.PubMedGoogle Scholar
  107. Shepherd, J., and Packard, C. J., 1986, Receptor independent low density lipoprotein catabolism, Methods Enzymol. 129: 566–590.PubMedGoogle Scholar
  108. Silverstein, S. C., Steinman, R. M., and Cohn, Z. A., 1977, Endocytosis, Annu. Rev. Biochem. 46: 669–722.PubMedGoogle Scholar
  109. Sinzinger, H., 1986, Role of platelets in atherosclerosis, Semin. Thromb. Haemostasis 12: 124–133.Google Scholar
  110. Slotte, P. J., Oram, J. F., and Bierman, E. L., 1987, Binding of high density lipoproteins to cell receptors promotes translocation of cholesterol from intracellular membranes to the cell surface, J. Biol. Chem 262: 12904–12907.PubMedGoogle Scholar
  111. Sparrow, C. P., Parthasarathy, S., and Steinberg, D., 1988, Enzymatic modification of low density lipoprotein by purified lipoxygenase plus phospholipase A2 mimics cell mediated oxidative modification, J. Lipid Res. 29: 745–753.PubMedGoogle Scholar
  112. Stein, O., Israeli, A., Leitersdorf, E., Halperin, G., and Stein, Y., 1986, Preferential uptake of cholesteryl esterHDL by cultured macrophages, Atherosclerosis 75: 151–158.Google Scholar
  113. Steinberg, D., 1986, Studies on the mechanism of action of probucol, Am. J. Cardiol. 57: 16H - 21H.PubMedGoogle Scholar
  114. Steinberg, D., Parthasarathy, S., Carew, T. E., Khor, J. C., and Witztum, J. L., 1989, Beyond cholesterol: modification of low density lipoproteins that increase its atherogenicity, N. Engl. J. Med. 320: 915–930.PubMedGoogle Scholar
  115. Steinberg, D., 1987, Lipoproteins and the pathogenesis of atherosclerosis, Circulation 76: 508–514.PubMedGoogle Scholar
  116. Steinbrecher, V. P., Fisher, M., Witztum, J. L., and Curtiss, L. K., 1984a, Immunogenicity of homologous low density lipoprotein after methylation, ethylation, acetylation or carbomylation generation of antibodies specific for derivatized lysine, J. Lipid Res. 25: 1109–1116.PubMedGoogle Scholar
  117. Steinbrecher, V. P., Parthasarathy, S., Leake, D. S., Witztum, J. L., and Steinberg, D., 1984b, 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.PubMedGoogle Scholar
  118. Steinbrecher, V. P., and Witztum, J. L., 1984c, Glucosylation of low density lipoproteins to an extent comparable to that seen in diabetes slows their catabolism, Diabetes 33: 130–134.PubMedGoogle Scholar
  119. Steinbrecher, V. P., Witztum, J. L., Parthasarathy, S., and Steinberg, D., 1987, Decreased in reactive amino groups during oxidation or endothelial cell modification of LDL, Arteriosclerosis 7: 135–143.PubMedGoogle Scholar
  120. Suits, A. G., Chait, A., Aviram, M., and Heinecke, J. W. 1989, Phagocytosis of aggregated lipoprotein by macrophages: Role of the low density lipoprotein receptor in foam cell formation, Proc. Natl. Acad. Sci. USA 86: 2713–2717.PubMedGoogle Scholar
  121. Tabas, I., and Boykow, G. C., 1987, Protein synthesis inhibition in mouse peritoneal macrophages results in increased acyl coenzyme A: Cholesterol acyl transferase activity and cholesteryl ester accumulation in the presence of native low density lipoprotein, J. Biol. Chem. 262: 12175–12181.PubMedGoogle Scholar
  122. Tabas, I., Weiland, D. A., and Tall, A. R., 1985, Unmodified low density lipoprotein causes cholesteryl ester accumulation in J774 macrophages, Proc. Natl. Acad. Sci. USA 82: 416–420.PubMedGoogle Scholar
  123. Tabas, I., Weiland, D. A., and Tall, A. R., 1986, Inhibition of acyl coenzyme A: Cholesterollacyl transferase in J774 macrophages enhances down regulation of the low density lipoprotein receptor and 3-hydroxy-3 methylglutaryl coenzyme A reductase and prevents low density lipoprotein-induced cholesterol accumulation, J. Biol. Chem. 261: 3147–3155.PubMedGoogle Scholar
  124. Tabas, I., Boykow, G. C., and Tall, A. R., 1987, Foam cell forming J774 macrophages have markedly elevated acyl coenzyme A: Cholesterol acyl transferase activity compared with mouse peritoneal macrophages in the presence of LDL despite similar LDL receptor activity. J. Clin. Invest. 79: 418–426.PubMedGoogle Scholar
  125. Traber, M. G., Brandon, K., and Kayden, H. J., 1983, Localization of the binding sites of native and acetylated low density lipoprotein (LDL) in human monocyte-derived macrophages, Exp. Cell Res. 148: 281–292.PubMedGoogle Scholar
  126. Triau, J. E., Meydani, S. N., Meydani, M., Libby, P., and Schaefer, E. J., 1986, Oxidized low density lipoproteins stimulate prostacyclin production by adult human vascular endothelial cells, Fed. Proc. 45: 347.Google Scholar
  127. Van Berkel, J. J. C., Nagelkeske, J. F., Harkes, L., and Kruijt, J. K., 1982, Processing of acetylated human low density lipoprotein by parenchymal and nonparenchymal cells, Biochem. J. 208: 493–503.PubMedGoogle Scholar
  128. Van Lenten, B. J., Fogelman, A. M., Jackson, R. J., Shapiro, S., Haberland, M. E., and Edwards, P. A., 1985, Receptor-mediated uptake of remnant lipoproteins by cholesterol-loaded human monocyte-macrophages, J. Biol. Chem. 260: 8783–8788.PubMedGoogle Scholar
  129. Viener, A., Aviram, M., and Brook, J. G., 1984, Abnormal plasma lipoprotein composition in hypercholesterolemic patients induces platelet activation, Eur. J. Clin. Invest. 14: 207–213.PubMedGoogle Scholar
  130. von Hodenberg, E., Khoo, J. C., Jensen, D., Witztum, J. L., and Steinberg, D., 1984, Mobilization of stored triglycerides from macrophages as free fatty acids, Arteriosclerosis 4: 630–635.Google Scholar
  131. Wang-Iverson, P., Ginsburg, H. N., Petanu, L. A., Le N. A., and Brown, W. V., 1985, Apo E mediated uptake and degradation of normal very low density lipoproteins by human monocyte/macrophages: A saturable pathway distinct from the LDL receptor, Biochem. Biophys. Res. Commun. 126: 578–586.PubMedGoogle Scholar
  132. Weksler, B. B., and Nachman, R. L., 1981, Platelets and atherosclerosis, Am. J. Med. 71: 331–333.PubMedGoogle Scholar
  133. White, J. G., 1977, Interaction of membrane systems in blood platelets, Am. J. Pathol. 66: 295–312.Google Scholar
  134. Wong, H., and Hashimoto, S., 1987, Accumulation of cholesteryl ester and lipid droplets in macrophages after uptake of cholesterol-rich necrotic products, Arteriosclerosis 7: 185–190.PubMedGoogle Scholar
  135. Y1ä-Herttuala, S., Jaakkola, O., Solakivi, T., Juivanieme, H., and Nikkari, T., 1986, The effect of proteoglycans, collagen and lysyl oxidase on the metabolism of low density lipoprotein by macrophages, Atherosclerosis 62: 73–80.PubMedGoogle Scholar
  136. Yokode, M., Ishii, K., Kume, N., Nogano, Y., Narumeija, S., and Kita, T., 1987, Oxidized LDL may be recognized at least by two binding sites on macrophages, Arteriosclerosis 7: 548a.Google Scholar
  137. Yokode, M., Kita, T., Kikawa, Y., Ogorochi, T., Narimiya, S., and Kawai, C., 1988, Stimulated anachidonate metabolism during foam cell lipoprotein, J. Clin. Invest. 81: 720–729.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Michael Aviram
    • 1
  1. 1.Lipid Research Laboratory, Rambam Medical Center, and Rappaport Institute for Research in the Medical SciencesTechnion Faculty of MedicineHaifaIsrael

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