Short- and long-term elevation of autoantibody titers against oxidized LDL in patients with acute coronary syndromes. Role of the lipoprotein-associated phospholipase A2 and the effect of atorvastatin treatment.
Oxidized low-density lipoprotein (oxLDL) is immunogenic while oxidized phospholipids (oxPL) formed on oxLDL and lysophosphatidylcholine (lyso-PC) generated during LDL oxidation through the hydrolysis of oxPL by the lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), significantly contribute to oxLDL immunogenicity. We determined the autoantibody titers against various forms of mildly oxLDL in patients with acute coronary syndromes without persistent elevation of the ST segment (NSTE-ACS) and with undetectable serum levels of lipoprotein (a). Moreover, the effect of early atorvastatin administration on these autoantibody titers was evaluated. From the 133 consecutive NSTE-ACS patients, 55 were eligible for the study. Thirty-four received atorvastatin (group A), whereas 21 did not received any hypolipidemic therapy (group B). Two forms of copper-oxidized LDL were prepared at the end of propagation or decomposition phase (oxLDL(P) or oxLDL(D), respectively). Similar types of oxLDL were prepared after previous inactivation of the endogenous Lp-PLA(2) [oxLDL(-)]. In group B, autoantibody titers of IgG class against oxLDL(P) and oxLDL(D) were elevated at 1 month of follow-up to reach the baseline values 3 months afterwards. By contrast the titers against oxLDL(-)(P) and oxLDL(-)(D) increased at 1 month of follow-up and remained elevated for up to 6 months of follow-up. Atorvastatin treatment prevented the elevation of autoantibody titers against all forms of oxidized LDL. We conclude that a short-term immune response against oxLDL(P) and oxLDL(D) (enriched in lyso-PC) and a chronic immune response against oxLDL(-)(P) and oxLDL(-)(D) (enriched in oxPL) are observed after an NSTE-ACS, suggesting an important role of the LDL-associated Lp-PLA(2) in modulating these immune responses. Early atorvastatin treatment prevents both immune responses; however, the clinical significance of this effect remains to be established.
Papathanasiou
Athanasios I
AI
Department of Cardiology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece.
Lourida
Evangelia S
ES
Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece.
Tsironis
Loukas D
LD
Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece.
Goudevenos
John A
JA
Department of Cardiology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece.
Tselepis
Alexandros D
AD
Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece. Electronic address: atselep@uoi.gr.
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000187:drug effects; D054058:Acute Coronary Syndrome / Q000097:blood / Q000276:immunology*; D000368:Aged; D000069059:Atorvastatin; D001323:Autoantibodies / Q000187:drug effects*; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology*
D001323:Autoantibodies; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007074:Immunoglobulin G; D008077:Lipoproteins, LDL; D011758:Pyrroles; C099252:oxidized low density lipoprotein; D000069059:Atorvastatin; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase