P195	Autoantibody titers against various forms of modified LDL in patients with stable angina are influenced by the lipoprotein-associated phospholipase A2 (PAF-acetylhydrolase) activity and the extent of oxidation.
1A.Papathanasiou, 2E.Lourida, 1J.Goudevenos, 2A.Tselepis
1Dept of Cardiology, School of Medicine, University of Ioannina, Ioannina, GR; 2Lab of Biochemistry, Dept of Chemistry, University of Ioannina, Ioannina, GR.

Objective: The oxidation of LDL induces immunogenic epitopes, many of which are due to oxidatively modified phospholipids (oxPL). Lysophosphatidylcholine (lyso-PC) is enzymatically generated during LDL oxidation through the hydrolysis of oxPL by the PAF-acetylhydrolase (PAF-AH). We studied the role of PAF-AH and the extent of LDL oxidation on the autoantibody titers in patients with stable angina. Methods and Results: 65 patients with stable angina and 47 age- and sex- matched healthy volunteers, participated in the study. Copper-oxidized LDL, at the end of the lag, propagation or decomposition phase (oxLDLL, oxLDLP and oxLDLD, respectively) and malondialdehyde-modified LDL (MDA-LDL) were used as antigens. Similar types of oxidized LDL were prepared after previous inactivation of endogenous PAF-AH [oxLDL(-)]. In both groups autoantibody titers against each type of oxLDL(-) were higher compared to the respective type of oxLDL. In both groups autoantibody titers were higher when the oxLDLP and oxLDLD or the respective types oxLDL(-) were used as antigens compared to oxLDLL or to oxLDL(-)L, respectively. Patients had significantly higher titers against all types of oxLDL (enriched in lyso-PC) and oxLDL(-) (enriched in intact oxPL), compared to controls (TAB1).In multivariate logistic regression analysis autoantibody titers against oxLDLP are associated with a significantly higher risk for coronary artery disease.   Controls (n=47) CAD patients(n=65) P values OxLDLL 0.873 ± 0.154 1.102 ± 0.191 0.001 OxLDLP 0.915 ± 0.243 1.197 ± 0.216 0.0005 OxLDLD 0.969 ± 0.180 1.209 ± 0.277 0.002 OxLDL (-)L 1.043 ± 0.226 1.334 ± 0.234 0.0001 OxLDL (-)P 1.154 ± 0.249 1.567± 0.232 0.0001 OxLDL (-)D 1.270 ± 0.269 1.570 ± 0.304 0.001 MDA-LDL 1.282 ± 0.205 1.298 ± 0.329 NS Conclusions:The PAF-AH activity as well as the extent of LDL oxidation may play important roles in the immunogenicity of oxidized LDL. Lyso-PC, a major component of oxLDLP, could be responsible for the elevated autoantibody titers against oxLDL in patients with stable angina.

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