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Arch Hellen Med, 23(1), January-February 2006, 63-71


Endogenous PAF-acetylhydrolase affects the antigenicity of oxidized LDL
in patients with coronary artery disease

1Laboratory of Biochemistry, Department of Chemistry,
2Department of Cardiology, Medical School, University of Ioannina, Ioannina, Greece

OBJECTIVE The oxidative modification of LDL induces immunogenic epitopes, many of which are due to phospholipids formed during oxidation, such as oxidized phosphatidylcholine (oxPC), lysophosphatidylcholine (lyso-PC), platelet activating factor (PAF) and oxidized phospholipids. Lyso-PC is enzymatically generated during LDL oxidation through the hydrolysis of oxidized phospholipids by the LDL-associated PAF-acetylhydrolase (PAF-AH). The aim of this study was to evaluate the autoantibody titers against oxLDL in relation to the phase of LDL oxidation and to the activity of the LDL-associated PAF-AH in patients with coronary artery disease, in order to investigate a possible role of this enzyme in the immunogenicity of oxLDL.

METHOD The autoantibody titers against various forms of oxLDL were estimated in 65 patients with stable angina pectoris and angiographically verified coronary artery disease (CAD) (7 women, 58 men, mean age 62.5±9.5 years) and in 47 healthy volunteers (control group). LDL isolated from fresh plasma was oxidized in the presence of 5 μΜ CuSO4. Three different forms of oxLDL were prepared, oxLDLL, oxLDLP and oxLDLD, i.e. at the end of the lag, propagation and decomposition phases, respectively. The same forms were also prepared after inactivation of endogenous PAF-AH [oxLDL(-)]. Malondialdehyde-modified LDL (MDA-LDL) was prepared and used as antigen. Autoantibody titers were measured by ELISA.

RESULTS CAD patients had significantly higher titers than controls against oxLDLL (1.102±0.391 vs 0.873±0.254, P<0.001), oxLDLP (1.223±0.340 vs 0.915±0.24, P<0.0001), oxLDLD (1.199±0.397 vs 0.969±0.280, P=0.002), oxLDLD(-)L (1.368±0.392 vs 1.043±0.226, P<0.0001), oxLDLD(-)P (1.567±0.332 vs 1.154±0.269, P<0.0001), and oxLDLD(-)D (1.563±0.320 vs 1.270±0.269, P<0.0001). By contrast, the autoantibody titers against MDA-LDL did not differ between CAD patients and controls. On multivariate logistic regression analysis after adjustment for other risk factors only elevated levels of oxLDLP and oxLDLD(-)P were associated with a significantly higher risk for CAD (RR=0.076, 0.012-0.478 95%CI, P=0.006, and RR=0.150, 0.035-0.641 95%CI, P=0.010, respectively).

CONCLUSIONS This study shows for the first time that autoantibodies against oxidized phosholipids and lyso-PC are observed in the serum of both patients with CAD and healthy subjects. Lyso-PC is probably the epitope that discriminates patients from healthy subjects. These findings indicate the significant role of PAF-AH as regards the type of epitopes formed in oxLDL, and consequently the type of autoantibodies formed against this atherogenic lipoprotein. Moreover, this study shows that autoantibodies to oxLDLP constitute an independent risk factor for cardiovascular disease.

Key words: Antibodies, Coronary disease, Lipoproteins.

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