Abstract
Atherosclerotic vascular disease is the leading cause of death in industrialized society. One important risk factor for the onset of atherosclerosis is an elevated concentration of low density lipoprotein (LDL), the major carrier of blood cholesterol (1). It is thus paradoxical that LDL often fails to exert atherogenic effects in vitro. These observations led to the suggestion that LDL has to be modified to promote vascular disease (2,3). Subsequent studies indicate that cultured arterial cells modify LDL (4) and that the mechanism involves oxidative damage (5–7). Oxidized LDL, but not native LDL, exerts a multitude of potentially atherogenic effects in vitro and in vivo (8,9), suggesting that oxidation might be a physiologically relevant pathway for LDL modification in the artery wall.
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References
Brown MS, Goldstein JL. Koch’s postulates for cholesterol. Cell. 1992;71:187.
Goldstein JL, Ho YK, Basu SK, Brown MS. Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc Natl Acad Sci USA. 1979;76:333.
Fogelman AM, Shechter I, Seager J, Hokom M, Child JS, Edwards PA. Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in human monocyte-macrophages. Proc Natl Acad Sci USA. 1980;77:2214.
Henriksen T, Mahoney EM, 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 USA. 1981;78:6499.
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. 1984;74:1890.
Morel DW, DiCorleto PE, Chisolm GM. Endothelial and smooth muscle cells alter low density lipoprotein in vitro by free radical oxidation. Arteriosclerosis. 1984;4:357.
Steinbrecher UP, Parthasarathy S, Leake DS, Witztum JL, Steinberg D. Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci USA. 1984;81:3883.
Witztum JL, Steinberg D. Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest. 1991;88:1785.
Berliner JA, Heinecke JW. The role of oxidized lipoproteins in atherogenesis. Free Rad Biol Med. 1996;20:707
Esterbauer H, Gebicki J, Puhl H, Jurgens G: The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Rad Biol Med. 1992; 13:341.
Daugherty A, Zweifel BS, Sobel BE, Schonfeld G. Isolation of low density lipoprotein from atherosclerotic vascular tissue of Watanabe Heritable Hyperlipidemic rabbits. Arteriosclerosis. 1988;8:768.
Yla-Herttuala S, Palinski W, Rosenfeld ME, Parthasarathy S, Carew TE, Butler S, Witztum JL, Steinberg D. Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man. J Clin Invest. 1989;84:1086.
Haberland ME, Cheng L, Fong D. Malondialdehyde-altered protein occurs in atheroma of Watanabe Heritable hyperlipidemic rabbits. Science. 1988;241:215.
Rosenfeld ME, Palinski W, Yla-Herttuala S, Butler S, Witztum JL. Distribution of oxidation specific lipid-protein adducts and apolipoprotein-B in atherosclerotic lesions of varying severity from WHHL rabbits. Arteriosclerosis. 1990; 10:336.
Steinberg D. Clinical trials of antioxidants in atherosclerosis: Are we doing the right thing? Lancet. 1995;346:36.
Diaz MN, Frei B, Vita JA, Keaney JF. Antioxidants and atherosclerotic heart disease. N Eng J Med. 1997;337:408.
Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ, Brown MJ. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet. 1996;347:781.
Frei B, Stocker R, Ames, BN, Antioxidant defenses and lipid peroxidation in human blood plasma. Proc Natl Acad Sci USA. 1988;85:9748.
Ehrenwald E, Chisolm GM, Fox PL. Intact ceruloplasmin oxidatively modifies low density lipoprotein. J Clin Invest. 1994;93:1493.
Balla G, Eaton JW, Belcher JD, Vercellotti GM. Hemin: A possible physiological mediator of low density lipoprotein oxidation and endothelial injury. Arterioscler Thromb. 1991;11:1700.
Thomas JP, Kalyanaraman B, Girotti W. Involvement of preexisting lipid hydroperoxides in Cu2+-stimulated oxidation of low-density lipoprotein. Arch Biochem Biophysics. 1994;315:244.
Bowry VW, Stanley KK, Stocker R. High density lipoprotein is the major carrier of lipid hydroperoxides in human blood plasma of fasting donors. Proc Natl Acad Sci USA. 1992;89:10316.
Hodis HN, Kramsch DM, Avogaro P, Bittolo-Bon G, Cazzolato G, Hwang J, peterson H, Sevanian A. Biochemical and cytotoxic characteristics of an in vivo circulating oxidized low density lipoprotein (LDL-). J. Lipid Res. 1994;35:669.
Smith C, Mitchinson MJ, Aruoma OI, Halliwell B. Stimulation of lipid peroxidation and hydroxyl radical generation by the contents of human atherosclerotic lesions. Biochem J. 1992;286:901.
Swain J, Gutteridge JMC. Prooxidant iron and copper, with ferroxidase and xanthine oxidase activity in human atherosclerotic material. FEBS Let. 1995;368:513.
Lamb D, Mitchinson MJ, Leake DS. Transition metals within human atherosclerotic lesions can catalyze the oxidation of low density lipoprotein by macrophages. FEBS Let. 1995;374:12.
Aasa R, Malmstrom BG, Saltman P, Vanngard T. The specific binding of iron (III) and copper (II) to transferrin and conalbumin. Biochem Biophys Acta. 1963;75:203.
Thomas CE. The influence of medium components on Cu-dependent oxidation of low density lipoproteins and its sensitivity to Superoxide dismutase. Biochim Biophys Acta. 1992;1128:50.
Peters T Jr, Blumenstock FA. Copper-binding properties of bovine serum albumin and its amino-terminal peptide fragment. J Biol Chem. 1967;242:1574.
Ascherio A, Willett WC. Are body iron stores related to the risk of coronary heart disease? N Eng J Med. 1994;330:1152.
Bothwell TH, Charlton RW, Cook JD, Finch CA. Iron metabolism in man. 1979; Oxford: Blackwell Scientific Pub.
Miller M, Hutchins GM. Hemochromatosis, multiorgan hemosiderosis, and coronary artery disease. JAMA. 1994;272:231.
Dabbagh AJ, Shwaery GT, Keaney JF, Frei B. Effect of iron overload and iron deficiency on atherosclerosis in the hypercholesterolemic rabbit. Arterioscler Thromb Vasc Biol. 1997;17:2638.
Araujo JA, Romano EL, Brito BE, Parthe V, Romano M, Bracho M, Montano RF, Cardier J: Iron overload augments the development of atherosclerotic lesions in rabbits. Arterioscler Thromb Vasc Biol. 1995; 15:1172.
Danks DM. Disorders of copper transport. In: Scriver, C.R., Beaudet, A.L. Sly, W.S., Valley, D. Eds. The metabolic basis of inherited disease. 6th ed. New York: McGraw-Hill, Inc. 1989:1411.
Heinecke JW. Mechanisms of oxidative damage of low density lipoprotein in human atherosclerosis. Cur Opin Lipid. 1997;8:268.
Lynch SM, Frei B. Mechanisms of copper-dependent and iron-dependent oxidative modification of human low density lipoprotein. J Lipid Res. 1993;34:1745.
Leuwenburgh C, Rasmussen JE, Hsu FF, Mueller DM, Pennathur S, Heinecke JW. Mass spectrometric quantification of markers for protein oxidation by tyrosyl radical, copper, and hydroxyl radical in low density lipoprotein isolated from human atherosclerotic plaques. J Biol Chem. 1997;272:3520.
Huggins TG, Wells-Knecht MC, Detorie NA, Baynes JW, Thorpe SR. Formation of otyrosine and dityrosine in proteins during radiolytic and metal-catalyzed oxidation. J Biol Chem. 1993;268:12341.
Fridovich I. The biology of oxygen radicals. Science. 1978;201:875.
Klebanoff SF. Oxygen metabolism and the toxic properties of phagocytes. Ann Int Med. 1980;93:480.
Hiramatsu K, Rosen H, Heinecke J, Wolfbauer G, Chait A. Superoxide initiates oxidation of low density lipoprotein by human monocytes. Arteriosclerosis. 1987;7:55.
Cathcart MK, McNally AK, Morel DW, Chisolm GM. Superoxide anion participation in human monocyte-mediated oxidation of LDL and conversion of LDL to a cytotoxin. J Immunol. 1989;142:1963.
Heinecke JW, Baker L, Rosen H, Chait A. Superoxide-mediated modification of low density lipoprotein by arterial smooth muscle cells. J Clin Invest. 1986;77:757.
Stenbrecher UP. Role of Superoxide in endothelial cell modification of LDL. Biochem Biophys Acta. 1988;959:20.
Mukhopadhyay CK, Ehrenwald E, Fox PL. Ceruloplasmin enhances smooth muscle cell-and endothelial cell-mediated low density lipoprotein oxidation by a superoxide-dependent mechanism. J Biol Chem. 1996;271:14773.
Bedwell SR, Dean T, Jessup W. The action of defined oxygen-centered radicals on human low-density lipoprotein. Biochem J. 1989;262:707.
Parthasarathy S, Weiland E, Steinberg D. A role for endothelial cell lipoxygenase in the oxidative modification of low density lipoprotein. Proc Natl Acad Sci USA. 1989;86:1046.
Jessup W, Simpson JA, Dean RT. Does Superoxide radical have a role in macrophage mediated oxidative modification of LDL? Atherosclerosis. 1993;99:107.
Rabini J, Klug-Roth D, Lilie J. Pulse radiolytic investigations of the catalyzed disproportionation of peroxy radicals. Aqueous cupric ions. J Phys Chem. 1973;77:1169.
Buettner GR. The pecking order of free radicals and antioxidants: Lipid peroxidation, alphatocopherol, and ascorbate. Arch Biochem Biophys. 1993;300:535.
Heinecke JW, Suzuki L, Rosen H, Chait A. The role of sulfur containing amino acids in Superoxide production and modification of low density lipoprotein by arterial smooth muscle cells. J Biol Chem. 1987;262:10098.
Parthasarthy S. Oxidation of low density lipoprotein by thiol compounds leads to its recognition by the acetyl-LDL receptor. Biochem Biophys Acta. 1987;917:337.
Heinecke JW, Kawamura M, Suzuki L, Chait A. Oxidation of low density lipoprotein by thiols: superoxide-dependent and-independent mechanisms. J Lipid Res. 1993;34:2051.
Sparrow CP, Olszewski J. Cellular oxidation of low density lipoprotein is caused by thiol production in media containing transition metal ions. J Lipid Res 1993;34:1219.
Lynch SM, Frei B. Physiological thiol compounds exert pro-and anti-oxidant effects, respectively, on iron-and copper-dependent oxidation of human low-density lipoprotein. Biochem Biophys Acta. 1997;1345:215.
Mudd SH, Levy HL, Skovby F. Disorders of transsulfuration. In: Scriver, CR, Beaudet AL, Sly WS, Valley D., eds. The metabolic basis of inherited disease. New York: McGraw-Hill.1989:793.
Mayer EL, Jacobsen DW, Robinson K. Homocysteine and coronary atherosclerosis. J Amer College Card. 1996;27:517.
Harker LA, Ross R, Slichter SJ, Scott CR. Homocystine-induced arteriosclerosis. J Clin Invest. 1976;58:731.
Dudman NPD, Wilcken DEL, Stocker R: Circulating lipid hydroperoxide levels in human homocysteinemia. Arterioscler Thromb. 1993; 13:512.
Yamamoto S. Mammalian lipoxygenases: Molecular structures and functions. Biochem Biophys Acta. 1992;1128:117.
Sparrow CP, Parthasarathy S, Steinberg D. Enzymatic modification of LDL by purified lipoxygenase plus phospholipase A2 mimics cell-mediated oxidative modification. J Lipid Res. 1988;29:745.
Parthasarathy S, Weiland E, Steinberg D. A role for endothelial cell lipoxygenase in the oxidative modification of low density lipoprotein. Proc Natl Acad Sci USA. 1989;86:1046.
Jessup W, Darley-Usmar V, O’Leary V, Bedwell OS. 5-Lipoxygenase is not essential for macrophage mediated oxidation of LDL. Biochem J. 1991;278:163.
Sparrow CP, Olszewski J. Cellular oxidative modification of LDL does not require lipoxygenases. Proc Natl Acad Sci USA. 1991;89:128.
Yla-Herttuala S, Rosenfeld ME, Parthasarathy S, Sigal E, Sarkioia T, Witztum JL, Steinberg D. Colocalization of 15-lipoxygenase mRNA and protein with epitopes of oxidized low density lipoprotein in macrophage-rich areas of atherosclerotic lesions. Proc Natl Acad Sci USA. 1987;87:6959.
Yla-Herttuala S, Luoma J, Viita H, Hiltunen T, Sisto T, Nikkari T. Transfer of 15-lipoxygenase gene into rabbit iliac arteries results in the appearance of oxidation-specific lipid-protein adducts characteristic of oxidized low density lipoprotein. J Clin Invest. 1995;95:2692.
Belkner J, Wiesner R, Rathman J, Barnett J, Sigal E, Kuhn H. Oxygenation of lipoproteins by mammalian lipoxygenases. Eur J Biochem. 1993;213:251.
Folcik VA, Nivar-Aristy RA, Krajewski LP, Cathcart MK. Lipoxygenase contributes to the oxidation of lipids in human atherosclerotic plaques. J Clin Invest. 1995;96:504.
Kuhn H, Heydeck D, Hugou I, Gniwotta C. In vivo action of 15-lipoxygenase in early stages of human atherosclerosis. J Clin Inves. 1997;99:888.
Rao SI, Wilks A, Hamberg M, Ortiz de Montellano PR. The lipoxygenase activity of myoglobin. J Biol Chem. 1994;269:7210.
Tillman C, Witztum JL, Rader DJ, Tangirala R, Fazio S, Linton MF, Funk CD. Disruption of the 12/15-lipoxygenase gene diminishes atherosclerosis in apo E-deficient mice. J Clin Invest. 1999; 103:1597.
Semenkovich CF, Heinecke JW. The mystery of diabetes and atherosclerosis: time for a new plot. Diabetes. 1997;46:327.
The Diabetes Control and Complication Trial. N Eng J Med. 1993;329:683.
Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes. 1991;40:405.
Bucala R, Cerami A. Advanced glycosylation: chemistry, biology, and implications for diabetes and aging. Adv Pharm. 1992;23:1.
Ahmed MU, Thorpe SR, Baynes JW. Identification of N-(carboxymethyl)-lysine as a degradation product of fructoselysine in glycated proteins. J Biol Chem. 1986;261:4889.
Dyer DG, Dunn JA, Thorpe SR, Bailie KE, Lyons TJ, McCance DR, Baynes JW. Accumulation of Mailard reaction products in skin collagen in diabetes and aging. J Clin Invest. 1993;91:2463.
Schleicher ED, Wagner E, Nerlich AG. Increased accumulation of the glycoxidation product N9epsilon)-(carboxymethyl) lysine in human tissues in diabetes and aging. J Clin Invest. 1997;99:457.
Moncada S, Palmer RM, Higgs EA. Nitric oxide: Physiology, pathophysiology and pharmacology. Pharmacol Rev. 1991;43:109.
Cooke JP, Tsao PS. Is NO an endogenous antiatherogenic molecule? Arterioscler Thromb. 1994;14:653.
Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and Superoxide. Proc Natl Acad Sci USA. 1990;87:1620.
Graham AN, Hogg N, Kalyanaraman B, O’Leary V, Darley-Usmar V, Moncade S. Peroxynitrite modifications of LDL leads to recognition by the macrophage scavenger receptor. FEBS. 1993;330:181.
Beckman JS, Chen J, Ischiropoulos H, Crow JP. Oxidative chemistry of peroxynitrite. Meth Enzym. 1994;233:229.
Beckman JS, Ye YZ, Anderson PG, Chen J, Accavitti MA, Tarpey MM, White CR. Extensive nitration of protein tyrosines in human atherosclerosis detected by immunohistochemistry. Biol Chem Hoppe-Seyler. 1994;375:81.
Jessup W, Mohr D, Gieseg SP, Dean RT, Stocker R. The participation of nitric oxide in cell free and its restriction of macrophage-mediated oxidation of low-density lipoprotein. Biochim Biophys Acta. 1992;1180:73.
Yates MT, Lambert LE, Whitten JP, MacDonald I, Mano M, Ku G, Mao SJT. A protective role for nitric oxide in the oxidative modification of low density lipoprotein by mouse macrophages. FEBS Lett. 1992;309:135.
Hogg N, Kalyanaraman B, Joseph J, Struck A, Parthasarathy S. Inhibition of low-density lipoprotein oxidation by nitric oxide: Potential role in atherogenesis. FEBS Lett. 1993;334:170.
Rubbo H, Parthasarathy S, Barnes S, Kirk M, Kalyanaraman B, Freeman BA. Nitric oxide inhibition of lipoxygenase-dependent liposome and low-density lipoprotein oxidation: Termination of radical chain propagation reactions and formation of nitrogen-containing oxidized lipid derivatives. Arch Biochem Biophys. 1995;324:1.
Aji W, Ravalli S, Szabolcs M, Jiang X-C, Sciacca RR, Michler RE, Canon PJ. L-arginine prevents Xanthoma development and inhibits atherosclerosis in LDL receptor knockout mice. Circulation. 1997;95:430.
Leeuwenburgh C, Hardy MM, Hazen SL, Wagner P, Oh-ishi S, Steinbrecher UP, Heinecke JW. Reactive nitrogen intermediates promote low density lipoprotein oxidation in human atherosclerosis. J Biol Chem. 1997;272:1433.
Gaziano JM, Hennekens CH. Vitamin antioxidants and cardiovascular disease. Cur Opin Lipidology. 1992;3:91.
Jha P, Flather M, Lonn E, Farkouh M, Yusuf S. The antioxidant vitamins and cardiovascular disease — a critical review of epidemiological and clinical trial data. Ann Int Med. 1995;123:860.
Bowry VW, Stocker R. Tocopherol-mediated peroxidation: the prooxidant effect of vitamin E on the radical-initiated oxidation of human low-density lipoprotein. J Am Chem Soc. 1993;115:6029.
Ingold KU, Bowry VW, Stocker R, Walling C. Autoxidation of lipids and antioxidation by alpha-tocopherol and ubiquinol in homogeneous solution and in aqueous dispersions of lipids-unrecognized consequences of lipid particle size as exemplified by oxidation of human low density lipoprotein. Proc Natl Acad Sci USA. 1993;90:45.
Lynch SM, Frei B. Reduction of copper, but not iron, by human low density lipoprotein (LDL)-implications for metal ion-dependent oxidative modification of LDL. J Biol Chem. 1995;270:5158.
Kontush A, Meyer S, Finckh B, Kohlschutter A, Beisiegel U. Alpha-tocopherol as a reductant for Cu(II) in human lipoproteins-triggering role in the initiation of lipoprotein oxidation. J Biol Chem. 1996;271:11106.
Shaish A, Daugherty A, O’Sullivan F, Schonfeld G, Heinecke JW. Beta-carotene inhibits atherosclerosis in hypercholesterolemic rabbits. J Clin Invest. 1995;96:2075.
Kleinveld HA, Demacker PNM, Stalenhoef AFH. Comparative study on the effect of lowdose vitamin E and probucol on the susceptibility of LDL to oxidation and the progression of atherosclerosis in Watanabe Heritable Hyperlipidemic rabbits. Arterioscler and Thromb. 1994;14:1386.
Kleinveld HA, Hak-Lemmers HLM, Hectors MPC, de Fouw NJ, Demacker PNM, Stalenhoef AFH: Vitamin E and fatty acid intervention does not attenuate the progression of atherosclerosis in Watanabe Heritable Hyperlipidemic rabbits. Arterioscler Thromb Vasc Biol. 1995; 15:290.
Hurst JK, Barette WC. Leukocytic oxygen activation and microbicidal oxidative toxins. CRC Critical Reviews Biochem Mol Biol. 1989;24:271.
Zeng J, Fenna RE. X-ray crystal structure of canine myeloperoxidase at 3 A resolution. J Mol Biol. 1992;226:185.
Daugherty A, Rateri DL, Dunn JL, Heinecke JW. Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions. J Clin Invest. 1994;94:437.
Heinecke JW, Li W, Daehnke HL, Goldstein JA. Dityrosine, a specific marker of oxidation, is synthesized by the myeloperoxidase-hydrogen peroxide system of human neutrophils and macrophages. J Biol Chem. 1993;268:4069.
Savenkova MI, Mueller DM, Heinecke JW. Tyrosyl radical generated by myeloperoxidase is a physiological catalyst for initiation of lipid peroxidation in low density lipoprotein. J Biol Chem. 1994;269:20394.
Karthein R, Dietz R, Nastainczyk W, Ruff H. Higher oxidation states of Prostaglandin H synthase. Eur J Biochem. 1988;171:313.
Heinecke JW, Li W, Francis GA, Goldstein JA. Tyrosyl radical generated by myeloperoxidase catalyzes the oxidative cross-linking of proteins. J Clin Invest. 1993;91:2866.
Francis GA, Mendez AJ, Bierman EL, Heinecke JW. Oxidative tyrosylation of high density lipoprotein by peroxidase enhances cholesterol removal from cultured fibroblasts and macrophage foam cells. Proc Natl Acad Sci USA. 1993;90:6631.
Harrison JE, Schultz J. Studies on the chlorinating activity of myeloperoxidase. J Biol Chem. 1976;251:1371.
Weiss SJ, Test ST, Eckmann CM, Ross D, Regiani S. Brominating oxidants generated by human eosinophils. Science. 1986;234:200.
Hazen SL, Hsu FF, Mueller DM, Crowley JR, Heinecke JW. Human neutrophils employ chlorine gas as an oxidant during phagocytosis. J Clin Invest. 1996;98:1283.
Hazen SL, Heinecke JW. 3-Chlorotyrosine, a specific marker of myeloperoxidase-catalyzed oxidation, is markedly elevated in low density lipoprotein isolated from human atherosclerotic intima. J Clin Invest. 1997;99:2075.
Eiserich JP, Cross CE, Jones AD, Halliwell B, Van der Vliet A. Formation of nitrating and chlorinating species by reaction of nitrite with hypochlorous acid: A novel mechanism for nitric oxide-mediated protein modification. J Biol Chem. 1996;271:19199.
Eiserich JP, Hristova M, Cross CE, Jones AD, Freeman BA, Halliwell B, Van der Vliet A. Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils. Nature. 1998;391:393.
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Heinecke, J.W. (2000). Sources of Vascular Oxidative Stress. In: Keaney, J.F. (eds) Oxidative Stress and Vascular Disease. Developments in Cardiovascular Medicine, vol 224. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4649-8_2
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