The low-density lipoprotein (LDL)-associated PAF-acetylhydrolase activity and the extent of LDL oxidation are important determinants of the autoantibody titers against oxidized LDL in patients with coronary artery disease.
The oxidation of low-density lipoprotein (LDL) induces immunogenic epitopes, many of which are due to oxidatively modified phospholipids (oxPL). Lysophosphatidylcholine (lyso-PC) which is generated during LDL oxidation through the hydrolysis of oxPL by LDL-associated PAF-acetylhydrolase (PAF-AH) is also immunogenic. We investigated whether the LDL-associated PAF-AH and the extent of LDL oxidation influence the autoantibody titers against oxidized LDL (oxLDL) in patients with stable angina as well as in apparently healthy volunteers. Three types of copper-oxidized LDL, were prepared at the end of the lag, propagation or decomposition phase (oxLDL(L), oxLDL(P) and oxLDL(D), respectively). Similar types of oxidized LDL were prepared after previous inactivation of endogenous PAF-AH [oxLDL(-)]. All these types of oxLDL as well as malondialdehyde-modified LDL (MDA-LDL) were used as antigens. Antibody titers against the above antigens were measured with an ELISA method in the serum of 65 patients with stable angina and 47 apparently healthy volunteers. Both groups exhibited higher autoantibody titers against each type of oxLDL(-) compared to the respective type of oxLDL (P<0.00001). In both groups autoantibody titers were higher when the oxLDL(P) and oxLDL(D) or oxLDL(-)(P) and oxLDL(-)(D) were used as antigens compared to oxLDL(L) (P<0.04) or to oxLDL(-)(L), respectively (P<0.0001 for all comparisons). Patients had significantly higher titers against all types of oxLDL (enriched in lyso-PC) and oxLDL(-) (enriched in intact oxPL) compared to controls. Autoantibody titers against MDA-LDL did not differ between patients and controls. Multivariate logistic regression analysis showed that among the autoantibody titers measured only those towards oxLDL(P) are associated with a significantly higher risk for coronary artery disease. LDL-associated PAF-AH activity may play an important role in decreasing the overall immunogenicity of oxLDL, whereas the extent of LDL oxidation seems to modulate the epitopes formed on oxLDL. Lyso-PC, a major component of oxLDL(P), could be mainly responsible for the elevated autoantibody titers against oxLDL in patients with stable angina.
Lourida
Evangelia S
ES
Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece.
Papathanasiou
Athanasios I
AI
Goudevenos
John A
JA
Tselepis
Alexandros D
AD
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood* / Q000378:metabolism; D000328:Adult; D000941:Antigens / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology*; D003324:Coronary Artery Disease / Q000097:blood* / Q000276:immunology*; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000097:blood* / Q000276:immunology*; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction
D000941:Antigens; D001323:Autoantibodies; D008077:Lipoproteins, LDL; D008246:Lysophospholipids; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C032881:lysophosphatidic acid