Background: Oxidized low-density lipoproteins (oxLDLs) play an important role in the progress of atherosclerosis. Autoantibodies (oxLDL Ab) against oxLDLs may reflect the extent of LDL oxidation in vivo. Our aim was to investigate the correlation between oxLDLs, oxLDL Ab and intima media thickness of the common carotid arteries (CCA-IMT) in a clinically healthy population. Methods: Two hundred subjects were recruited, and demographic and clinical characteristics of the subjects were recorded. By use of tertile classification of plasma oxLDLs and oxLDL Ab, 9 groups including 4 extreme subject groups were generated. CCA-IMT was measured as an indicator of carotid atherosclerosis. Results: Age and plasma LDL concentration contributed significantly to CCA-IMT (p < 0.05). Body mass index, smoking index and plasma LDL concentration were significantly positively related to the plasma oxLDLs concentration; by contrast, plasma oxLDL Ab were significantly negatively related to the plasma oxLDL concentration (p < 0.05). Subjects in the group with low oxLDL Ab/high oxLDLs had the greatest CCA-IMT and the highest level of LDL; by contrast, subjects in the group with high oxLDL Ab/low oxLDLs had the least CCA-IMT and the lowest level of LDL. Conclusions: Both plasma oxLDLs and oxLDL Ab contribute, although in opposite ways, to the LDL metabolism and development of atherosclerosis. Immune response to oxLDLs may exert a protective role at an early stage of atherosclerosis.

Braunwald E: Shattuck lecture – cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities. N Engl J Med 1997;337:1360–1369.
Willerson JT, Ridker PM: Inflammation as a cardiovascular risk factor. Circulation 2004;109(suppl 1):II2–II10.
Ridker PM, Rifai N, Rose L, Buring JE, Cook NR: Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 2002;347:1557–1565.
Parthasarathy S, Steinberg D, Witztum JL: The role of oxidized low-density lipoproteins in the pathogenesis of atherosclerosis. Annu Rev Med 1992;43:219–225.
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;84:1086–1095.
Lusis AJ: Atherosclerosis. Nature 2000;407:233–241.
Libby P, Ridker P, Maseri A: Inflammation and atherosclerosis. Circulation 2002;105:1135–1143.
Glass CK, Witztum JL: Atherosclerosis: the road ahead. Cell 2001;104:503–516.
Vaarala O: Antibodies to oxidised LDL. Lupus 2000;9:202–205.
Bonithon-Kopp C, Coudray C, Berr C, Touboul PJ, Feve JM, Favier A, Ducimetiere P: Combined effects of lipid peroxidation and antioxidant status on carotid atherosclerosis in a population aged 59–71 y: the EVA study. Am J Clin Nutr 1997;65:121–127.
Uusitupa MI, Nishanen L, Luoma J, Vilja P, Mercuri M, Rauramaa R, Yla-Herttuala S: Autoantibodies against oxidized LDL do not predict atherosclerotic vascular disease in non-insulin-dependent diabetes mellitus. Arterioscler Thromb Vasc Biol 1996;16:1236–1242.
Schumacher M, Eber B, Tatzber F, Kaufmann P, Halwachs G, Fruhwald FM, Zweiker R, Esterbauer H, Klein W: Transient reduction of autoantibodies against oxidized LDL in patients with acute myocardial infarction. Free Radic Biol Med 1995;18:1087–1091.
Ameli S, Hultgardh-Nilsson A, Regnstrom J, Calara F, Yano J, Cercek B, Shah PK, Nilsson J: Effect of immunization with homologous LDL and oxidized LDL on early atherosclerosis in hypercholesterolemic rabbits. Arterioscler Thromb Vasc Biol 1996;16:1074–1079.
de Oliveira FG, Rossi CL, de Oliveira MG, Saad MJ, Velloso LA: Effect of vitamin E supplementation on antibody levels against malondialdehyde modified LDL in hyperlipidemic hamsters. Cardiovasc Res 2000;47:567–573.
Palinski W, Tangirala, RK, Miller E, Young SG, Witztum JL: Increased autoantibody titers against epitopes of oxidized LDL in receptor-deficient mice with increased atherosclerosis. Arterioscler Thromb Vasc Biol 1995;15:1569–1576.
Salonen JT, Yla-Herttuala S, Yamamoto R, Butler S, Korpela H, Salonen R, Nvvssonen K, Palinski W, Witztum JL: Autoantibody against oxidised LDL and progression of carotid atherosclerosis. Lancet 1992;339:883–887.
Puurunen M, Manttari M, Manninen V, Tenkanen L, Alfthan G, Ehnholm C, Vaarala O, Aho K, Palosuo T: Antibody against oxidized low-density lipoprotein predicting myocardial infarction. Arch Intern Med 1994;154:2605–2609.
Dotevall A, Hulthe J, Rosengren A, Wiklund O, Wilhelmsen L: Autoantibodies against oxidized low-density lipoprotein and C-reactive protein are associated with diabetes and myocardial infarction in women. Clin Sci 2001;101:523–531.
Fang JC, Kinlay S, Behrendt D, Hikita H, Witztum JL, Selwyn AP, Ganz P: Circulating autoantibodies to oxidized LDL correlate with impaired coronary endothelial function after cardiac transplantation. Arterioscler Thromb Vasc Biol 2002;22:2044–2048.
Heitzer T, Yla-Herttuala S, Luoma J, Kurz S, Munzel T, Just H, Olschewski M, Drexler H: Cigarette smoking potentiates endothelial dysfunction of forearm resistance vessels in patients with hypercholesterolemia. Role of oxidized LDL. Circulation 1996;93:1346–1353.
Uusitupa MI, Niskanen L, Luoma J, Vilja P, Mercuri M, Rauramaa R, Yla-Herttuala S: Autoantibodies against oxidized LDL do not predict atherosclerotic vascular disease in non-insulin-dependent diabetes mellitus. Arterioscler Thromb Vasc Biol 1996;16:1236–1242.
van de Vijver LP, Steyger R, van Poppel G, Boer JM, Kruijssen DA, Seidell JC, Princen HM: Autoantibodies against MDA-LDL in subjects with severe and minor atherosclerosis and healthy population controls. Atherosclerosis 1996;122:245–253.
O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr: Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 1999;340:14–22.
Touboul PJ, Elbaz A, Koller C, Lucas C, Adrai V, Chedru F, Amarenco P: Common carotid artery intima-media thickness and brain infarction: the Etude du Profil Genetique de I’Infarctus Cerebral (GENIC) case-control study. The GENIC Investigators. Circulation 2000;102:313–318.
Tang R, Hennig M, Thomasson B, Scherz R, Ravinetto R, Catalini R, Rubba P, Zanchetti A, Bond MG: Baseline reproducibility of B-mode ultrasonic measurement of carotid artery intima-media thickness: the European Lacidipine Study on Atherosclerosis (ELSA). J Hypertens 2000;18:197–201.
Salonen JT, Salonen R: Ultrasound B-mode imaging in observational studies of atherosclerotic progression. Circulation 1993;87(suppl 3):II56–II65.
Salonen JT, Yla-Herttuala S, Yamamoto R: Autoantibody against oxidized LDL and progression of carotid atherosclerosis. Lancet 1992;339:883–887.
Esterbauer H, Gebicki J, Puhl H, Jurgens G: The role of lipid peroxidation in oxidative modification of LDL. Free Radic Res Commun 1992;13:341–390.
Liu CS, Chiang TH, Kuo CL, Ou CC, Lii CK, I SH, Wei YH, Chen HW: Contribution of plasma folic acid and homocysteine levels to the mean carotid intima media thickness in smokers. Nutr Res 2005;25:835–845.
Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;8:499–502.
Goldstein JL, Ho Y.K, 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;76:333–337.
Cominacini L, Garbin U, Pasini AF, Davoli A, Campagnola M, Contessi GB, Pastorino AM, Lo CV: Antioxidants inhibit the expression of intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 induced by oxidized LDL on human umbilical vein endothelial cells. Free Radic Biol Med 1997;22:117–127.
Cushing SD, Berliner JA, Valente AJ, Territo MC, Navab M, Parhami F, Gerrity R, Schwartz 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 1990;87:5134–5138.
Mertens A, Holvoet P: Oxidized LDL and HDL: antagonists in atherothrombosis. FASEB J 2001;15:2073–2084.
Stiko-Rahm A, Hultgardh-Nilsson A, Regnstrom J, Hamsten A, Nilsson J: Native and oxidized LDL enhances production of PDGF AA and the surface expression of PDGF receptors in cultured human smooth muscle cells. Arterioscler Thromb 1992;12:1099–1109.
Kohno M, Yokokawa K, Yasunari K, Minami M, Kano H, Hanehira T, Yoshikawa J: Induction by lysophosphatidylcholine, a major phospholipid component of atherogenic lipoproteins, of human coronary artery smooth muscle cell migration. Circulation 1998;98:353–359.
Kim JG, Taylor WR, Parthasarathy S: Demonstration of the presence of lipid peroxide-modified proteins in human atherosclerotic lesions using a novel lipid peroxide-modified anti-peptide antibody. Atherosclerosis 1999;143:335–340.
Lindner V, Lappi DA, Baird A, Majack RA, Reidy MA: Role of basic fibroblast growth factor in vascular lesion formation. Circ Res 1991;68:106–113.
Chambless LE, Heiss G, Folsom AR, Rosamond W, Szklo M, Sharrett AR, Clegg LX: Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987–1993. Am J Epidemiol 1997;146:483–494.
Poli A, Tremoli E, Colombo A, Sirtori M, Pignoli P, Paoletti R: Ultrasonographic measurement of the common carotid artery wall thickness in hypercholesterolemic patients. A new model for the quantitation and follow-up of preclinical atherosclerosis in living human subjects. Atherosclerosis 1988;70:253–261.
Junyent M, Cofan M, Nunez I, Gilabert R, Zambon D, Ros E: Influence of HDL cholesterol on preclinical carotid atherosclerosis in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 2006;26:1107–1113.
Grover S, Sinha RP, Singh U, Tewari S, Aggarwal A, Misra R: Subclinical atherosclerosis in rheumatoid arthritis in India. J Rheumatol 2006;33:244–247.
Ballantyne C, Arroll B, Shepherd J: Lipids and CVD management: towards a global consensus. Eur Heart J 2005;26:2224–2231.
Mackinnon AD, Jerrard-Dunne P, Sitzer M, Buehler A, von Kegler S, Markus HS: Rates and determinants of site-specific progression of carotid artery intima-media thickness: the carotid atherosclerosis progression study. Stroke 2004;35:2150–2154.
Jansen ACM, van Aalst-Cohen ES, Tanck MW, Trip MD, Lansberg PJ, Liem AH, Roeters van Lennep HWO, Sijbrands EJG, Kastelein JJP: The contribution of classical risk factors to cardiovascular disease in familial hypercholesterolemia: data in 2,400 patients. J Intern Med 2004;256:482–490.
de Luis DA, Aller R, Izaola O, Gonzalez Sagrado M, Conde R: Differences in glycaemic status do not predict weight loss in response to hypocaloric diets in obese patients. Clin Nutr 2006;25:117–122.
Brouwers A, Langlois M, Delanghe J, Billiet J, De Buyzere M, Vercaemst R, Rietzschel E, Bernard D, Blaton V: Oxidized low-density lipoprotein, iron stores, and haptoglobin polymorphism. Atherosclerosis 2004;176:189–195.
Bing H, Wang J, Zhang C, Cai H: Positive correlation between in vivo oxidized LDL and LDL immune complexes. Clin Biochem 2004;37:72–75.
Shoji T, Nishizawa Y, Fukumoto M, Shimamura K, Kimura J, Kanda H, Emoto M, Kawagishi T, Morii H: Inverse relationship between circulating oxidized low density lipoprotein (oxLDL) and anti-oxLDL antibody levels in healthy subjects. Atherosclerosis 2000;148:171–177.
Mosca L, Rubenfire M, Tarshis T, Tsai A, Pearson T: Clinical predictors of oxidized low-density lipoprotein in patients with coronary artery disease. Am J Cardiol 1997;80:825–830.
Miklund O, Witztum JL, Carew TE, Pittman RC, Elam RL, Steinberg D: Turnover and tissue sites of degradation of glucosylated low density lipoprotein in normal and immunized rabbits. J Lipid Res 1987;28:1098–1109.
Lopes-Virella MF, Binzafar N, Rackley S, Takei A, La Via M, Virella G: The uptake of LDL-IC by human macrophages: predominant involvement of the FcγRI receptor. Atherosclerosis 1997;135:161–170.
Klimov AN, Denisenko AD, Vinogradov AG, Nagarnev VA, Pivovarova YI, Sitnikova OD, Pleskov VM: Accumulation of CE in macrophages incubated with human lipoprotein-antibody autoimmune complex. Atherosclerosis 1988;74:41–46.
Bergmark C, Wu R, de Faire U, Lefvert AK, Swedenborg J: Patients with early-onset peripheral vascular disease have increased levels of autoantibodies against oxidized LDL. Arterioscler Thromb Vasc Biol 1995;15:441–445.
Maggi E, Chiesa R, Melissano G, Castellano R, Astore D, Grossi A, Finardi G, Bellomo G: LDL oxidation in patients with severe carotid atherosclerosis: a study of in vitro and in vivo oxidation markers. Arterioscler Thromb 1994;14:1892–1899.
Palinski W, Miller E, Witztum J: Immunization of low density lipoprotein (LDL) receptor deficient rabbits with homologous malondialdehyde-modified LDL reduces atherosclerosis. Proc Natl Acad Sci USA 1995;92:821–825.
Fukumoto M, Shoji T, Emoto M, Kawagishi T, Okuno Y, Nishizawa Y: Antibodies against oxidized LDL and carotid artery intima-media thickness in a healthy population. Arterioscler Thromb Vasc Biol 2000;20:703–707.
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