Oxidized lipoproteins in atherosclerosis and thrombosis

Oxidized low density lipoproteins (LDL) and autoimmune antibodies against oxidized LDL have been demonstrated in human atherosclerotic lesions; they may enhance the progression of these lesions by 1) enhancing monocyte adhesion and macrophage foam cell generation; 2) inducing smooth muscle cell migration, proliferation, and foam cell generation; 3) enhancing platelet adhesion and aggregation, which may stimulate macrophage foam cell generation and smooth muscle cell proliferation; 4) triggering thrombosis; and 5) impairing vasodilation, which results in increased shear stress. The oxidation of LDL probably occurs in the arterial wall, where it is sequestered from circulating antioxidants. Atherosclerotic arterial walls contain increased levels of redox‐active metal ions, and the LDL of patients with atherosclerotic cardiovascular disease are more susceptible to oxidation, possibly as a result of reduced endogenous antioxidants such as vitamin E. Dietary supplementation with vitamin E (up to 1,000 IU/day) or administration of probucol reduce the oxidation rate of LDL and may significantly decrease the risk of coronary heart disease.—Holvoet, P., Collen, D. Oxidized lipoproteins in atherosclerosis and thrombosis. FASEB J. 8, 1279‐1284 (1994)

[1]  Chen Kf.  Studies on the pathogenesis of atherosclerosis , 1989 .

[2]  K. Kugiyama,et al.  Transferable lipids in oxidized low-density lipoprotein stimulate plasminogen activator inhibitor-1 and inhibit tissue-type plasminogen activator release from endothelial cells. , 1993, Circulation research.

[3]  J L Witztum,et al.  Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[4]  D. Steinberg,et al.  Expression of monocyte chemoattractant protein 1 in macrophage-rich areas of human and rabbit atherosclerotic lesions. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[5]  G. Hansson,et al.  Immune mechanisms in atherosclerosis. , 1994, Coronary artery disease.

[6]  M. Davies,et al.  Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. , 1993, British heart journal.

[7]  P. Henriksson,et al.  The antioxidant butylated hydroxytoluene prevents early cholesterol-induced microcirculatory changes in rabbits. , 1994, The Journal of clinical investigation.

[8]  D. Steinberg,et al.  Feasibility of using an oleate-rich diet to reduce the susceptibility of low-density lipoprotein to oxidative modification in humans. , 1991, The American journal of clinical nutrition.

[9]  S. King,et al.  Probucol Decreases Neointimal Formation in a Swine Model of Coronary Artery Balloon Injury A Possible Role for Antioxidants in Restenosis , 1993, Circulation.

[10]  M. Brown,et al.  Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. , 1983, Annual review of biochemistry.

[11]  C. Sparrow,et al.  Cellular oxidative modification of low density lipoprotein does not require lipoxygenases. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[12]  R. Cohen,et al.  Preservation of Endothelium‐Dependent Relaxation in Atherosclerotic Rabbit Aorta by Probucol , 1993, Journal of cardiovascular pharmacology.

[13]  O. Quehenberger,et al.  Autoxidation of human low density lipoprotein: loss of polyunsaturated fatty acids and vitamin E and generation of aldehydes. , 1987, Journal of lipid research.

[14]  R. Ross.  The pathogenesis of atherosclerosis--an update. , 1986, The New England journal of medicine.

[15]  E. Rimm,et al.  Vitamin E consumption and the risk of coronary heart disease in men. , 1993, The New England journal of medicine.

[16]  J. Deckers,et al.  Retardation of angiographic progression of coronary artery disease by nifedipine , 1990, The Lancet.

[17]  S. Glagov,et al.  Arterial foam cells with distinctive immunomorphologic and histochemical features of macrophages. , 1980, The American journal of pathology.

[18]  R. Stocker,et al.  Inhibition by interferon-gamma of human mononuclear cell-mediated low density lipoprotein oxidation. Participation of tryptophan metabolism along the kynurenine pathway. , 1994, The Journal of clinical investigation.

[19]  K. Messmer,et al.  Superoxide-dependent stimulation of leukocyte adhesion by oxidatively modified LDL in vivo. , 1992, Arteriosclerosis and thrombosis : a journal of vascular biology.

[20]  P. Reaven,et al.  Effect of dietary antioxidant combinations in humans. Protection of LDL by vitamin E but not by beta-carotene. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[21]  D. Steinberg,et al.  Rabbit and human atherosclerotic lesions contain IgG that recognizes epitopes of oxidized LDL. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[22]  A. Hamsten,et al.  Native and oxidized LDL enhances production of PDGF AA and the surface expression of PDGF receptors in cultured human smooth muscle cells. , 1992, Arteriosclerosis and thrombosis : a journal of vascular biology.

[23]  M. Aviram,et al.  Phospholipase D-modified low density lipoprotein is taken up by macrophages at increased rate. A possible role for phosphatidic acid. , 1993, The Journal of clinical investigation.

[24]  D. Collen,et al.  Stimulation with a monoclonal antibody (mAb4E4) of scavenger receptor-mediated uptake of chemically modified low density lipoproteins by THP-1-derived macrophages enhances foam cell generation. , 1994, The Journal of clinical investigation.

[25]  T. Carlos,et al.  Membrane Proteins Involved in Phagocyte Adherence to Endothelium , 1990, Immunological reviews.

[26]  Vitamin E consumption and the risk of coronary disease in women. , 1993, The New England journal of medicine.

[27]  R. Krauss,et al.  Susceptibility of small, dense, low-density lipoproteins to oxidative modification in subjects with the atherogenic lipoprotein phenotype, pattern B. , 1993, The American journal of medicine.

[28]  M. Blombäck,et al.  PLASMINOGEN ACTIVATOR INHIBITOR IN PLASMA: RISK FACTOR FOR RECURRENT MYOCARDIAL INFARCTION , 1987, The Lancet.

[29]  W. Vetter,et al.  Oxidation of low density lipoprotein enhances its potential to increase intracellular free calcium concentration in vascular smooth muscle cells. , 1992, Arteriosclerosis and thrombosis : a journal of vascular biology.

[30]  R. Gerrity.  The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions. , 1981, The American journal of pathology.

[31]  K. Pritchard,et al.  Atherogenic levels of low-density lipoprotein increase endocytotic activity in cultured human endothelial cells. , 1992, The American journal of pathology.

[32]  A. Lusis,et al.  Induction of endothelial cell expression of granulocyte and macrophage colony-stimulating factors by modified low-density lipoproteins , 1990, Nature.

[33]  D. Steinberg,et al.  A role for endothelial cell lipoxygenase in the oxidative modification of low density lipoprotein. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[34]  P. Haslam,et al.  Enhancement of the antigen‐presenting function of monocytes by cholesterol: possible relevance to inflammatory mechanisms in extrinsic allergic alveolitis and atherosclerosis , 1992, Clinical and experimental immunology.

[35]  B. Hoffman,et al.  Inactivation of endothelial derived relaxing factor by oxidized lipoproteins. , 1992, The Journal of clinical investigation.

[36]  O. Aruoma,et al.  Stimulation of lipid peroxidation and hydroxyl-radical generation by the contents of human atherosclerotic lesions. , 1992, The Biochemical journal.

[37]  J L Witztum,et al.  Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man. , 1989, The Journal of clinical investigation.

[38]  H. Esterbauer,et al.  Effect of antioxidants on oxidative modification of LDL. , 1991, Annals of medicine.

[39]  M. Territo,et al.  Minimally modified low density lipoprotein stimulates monocyte endothelial interactions. , 1990, The Journal of clinical investigation.

[40]  D. A. Armstrong.  Oxidized LDL ceroid, and prostaglandin metabolism in human atherosclerosis. , 1992, Medical hypotheses.

[41]  J. Salonen,et al.  Autoantibody against oxidised LDL and progression of carotid atherosclerosis , 1992, The Lancet.

[42]  M. Reidy,et al.  Role of basic fibroblast growth factor in vascular lesion formation. , 1991, Circulation research.

[43]  T. Carew,et al.  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. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[44]  H F Hoff,et al.  Lesion-derived low density lipoprotein and oxidized low density lipoprotein share a lability for aggregation, leading to enhanced macrophage degradation. , 1991, Arteriosclerosis and thrombosis : a journal of vascular biology.

[45]  Yazaki,et al.  Oxidation-labile subfraction of human plasma low density lipoprotein isolated by ion-exchange chromatography. , 1991, Journal of lipid research.

[46]  E. Arbustini,et al.  Coronary atherosclerotic plaques with and without thrombus in ischemic heart syndromes: a morphologic, immunohistochemical, and biochemical study. , 1991, The American journal of cardiology.