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      Autoantibodies Against Oxidized Low-Density Lipoprotein and Cardiolipin in Patients With Coronary Heart Disease

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          Abstract

          Abstract —Autoantibodies against oxidized low density lipoprotein (oxLDL) have been proposed to be independent predictors of atherosclerotic vascular disease. Because the levels of autoantibodies against oxLDL and cardiolipin might be modified by the presentation and severity of coronary heart disease (CHD), we measured their levels in patients with different manifestations of CHD (n=415, mean age 61 years, range 33 to 74 years) in a subset of the European Action on Secondary Prevention through Intervention to Reduce Events (EUROASPIRE) study. There were 109 patients with coronary artery bypass surgery, 106 patients with balloon angioplasty, 101 patients with acute myocardial infarction, and 99 patients with acute myocardial ischemia. Autoantibodies were measured by ELISA. Food records and fatty acid profiles of serum cholesteryl esters were used to evaluate dietary intake. Anti-oxLDL antibodies were significantly higher in the group with acute myocardial infarction than in other groups in men (coronary artery bypass surgery 1.91±1.41, balloon angioplasty 2.11±2.19, acute myocardial infarction 2.52±2.05, and acute myocardial ischemia 1.96±1.78; P =0.022, mean±SD) but not in women. The titers of anti-cardiolipin antibodies did not differ among the patient groups. Neither of the autoantibodies was associated with recurrent coronary events. Anti-oxLDL and anti-cardiolipin autoantibodies were not correlated with serum total cholesterol, high density lipoprotein cholesterol, or triglycerides, except that in women anti-oxLDL antibodies and triglycerides were positively correlated ( r =0.225, P =0.011). In men, anti-cardiolipin antibodies were higher in the lowest quartiles of dietary intakes of vitamin E and polyunsaturated fat. Dietary intakes of vitamin E and polyunsaturated fat were correlated ( r =0.588, P <0.001). In conclusion, autoantibodies against oxLDL were associated with myocardial infarction in men. Anti-cardiolipin autoantibodies were inversely correlated with dietary intakes of vitamin E and polyunsaturated fat in men with CHD.

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          Most cited references27

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          Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man.

          Three lines of evidence are presented that low density lipoproteins gently extracted from human and rabbit atherosclerotic lesions (lesion LDL) greatly resembles LDL that has been oxidatively modified in vitro. First, lesion LDL showed many of the physical and chemical properties of oxidized LDL, properties that differ from those of plasma LDL: higher electrophoretic mobility, a higher density, higher free cholesterol content, and a higher proportion of sphingomyelin and lysophosphatidylcholine in the phospholipid fraction. A number of lower molecular weight fragments of apo B were found in lesion LDL, similar to in vitro oxidized LDL. Second, both the intact apo B and some of the apo B fragments of lesion LDL reacted in Western blots with antisera that recognize malondialdehyde-conjugated lysine and 4-hydroxynonenal lysine adducts, both of which are found in oxidized LDL; plasma LDL and LDL from normal human intima showed no such reactivity. Third, lesion LDL shared biological properties with oxidized LDL: compared with plasma LDL, lesion LDL produced much greater stimulation of cholesterol esterification and was degraded more rapidly by macrophages. Degradation of radiolabeled lesion LDL was competitively inhibited by unlabeled lesion LDL, by LDL oxidized with copper, by polyinosinic acid and by malondialdehyde-LDL, but not by native LDL, indicating uptake by the scavenger receptor(s). Finally, lesion LDL (but not normal intimal LDL or plasma LDL) was chemotactic for monocytes, as is oxidized LDL. These studies provide strong evidence that atherosclerotic lesions, both in man and in rabbit, contain oxidatively modified LDL.
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            Autoantibody against oxidised LDL and progression of carotid atherosclerosis

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              Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H).

              Anti-phospholipid (aPL) antibodies that exhibit binding in cardiolipin (CL) ELISA can be purified to greater than 95% purity by sequential phospholipid affinity and ion-exchange chromatography. However, these highly purified aPL antibodies do not bind to the CL antigen when assayed by a modified CL ELISA in which the blocking agent does not contain bovine serum, nor do they bind to phospholipid affinity columns. Binding to the phospholipid antigen will only occur if normal human plasma, human serum, or bovine serum is present, suggesting that the binding of aPL antibodies to CL requires the presence of a plasma/serum cofactor. Using sequential phospholipid affinity, gel-filtration, and ion-exchange chromatography, we have purified this cofactor to homogeneity and shown that the binding of aPL antibodies to CL requires the presence of this cofactor in a dose-dependent manner. N-terminal region sequence analysis of the molecule has identified the cofactor as beta 2-glycoprotein I (beta 2GPI) (apolipoprotein H), a plasma protein known to bind to anionic phospholipids. These findings indicate that the presence of beta 2GPI is an absolute requirement for antibody-phospholipid interaction, suggesting that bound beta 2GPI forms the antigen to which aPL antibodies are directed. Recent evidence indicates that beta 2GPI exerts multiple inhibitory effects on the coagulation pathway and platelet aggregation. Interference with the function of beta 2GPI by aPL antibodies could explain the thrombotic diathesis seen in association with these antibodies.
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                Author and article information

                Journal
                Arteriosclerosis, Thrombosis, and Vascular Biology
                ATVB
                Ovid Technologies (Wolters Kluwer Health)
                1079-5642
                1524-4636
                January 2000
                January 2000
                : 20
                : 1
                : 204-209
                Affiliations
                [1 ]From the Department of Clinical Nutrition (A.T.E., M.I.J.U.), the A.I. Virtanen Institute of Molecular Sciences (O.N., S.Y.-H.), and the Department of Medicine (S.L., S.Y.-H.), University of Kuopio, Kuopio, Finland.
                Article
                10.1161/01.ATV.20.1.204
                7469c1de-b1b0-485e-a1a8-5d91cf32c633
                © 2000
                History

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