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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

      Abstract

      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 A2 (Lp-PLA2), 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 hypolipdemic therapy (group B). Two forms of copper-oxidized LDL were prepared at the end of propagation or decomposition phase (oxLDLP or oxLDLD, respectively). Similar types of oxLDL were prepared after previous inactivation of the endogenous Lp-PLA2 [oxLDL(−)]. In group B, autoantibody titers of IgG class against oxLDLP and oxLDLD 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 oxLDLP and oxLDLD (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-PLA2 in modulating these immune responses. Early atorvastatin treatment prevents both immune responses; however, the clinical significance of this effect remains to be established.

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