Circulating autoantibodies to oxidized cardiolipin correlate with isoprostane F-2 alpha-VI levels and the extent of atherosclerosis in ApoE-deficientmice: modulation by vitamin E

Lipid peroxidation plays an important role in atherogenesis, Previous studi es suggested that autoantibodies against epitopes of oxidized low-density l ipoprotein may indicate the extent or rate of progression of atherosclerosi s, The aim of this study was to investigate whether autoantibodies to oxidi zed phospholipids, such as oxidized cardiolipin (OxCL), correlate with leve ls of isoprostane F-2 alpha-VI, a sensitive marker of in vivo lipid peroxid ation, as well as with the extent of atherosclerosis, Two groups of apolipo protein E-deficient mice were fed chow with or without vitamin E (2000 IU/k g diet) for 16 weeks. In untreated animals, autoantibodies against OxCL and urinary, plasma, and aortic isoprostane F-2 alpha-VI levels increased sign ificantly, Vitamin E treatment significantly reduced antibody titers, isopr ostane levels, and atherosclerosis at the end of the study, compared with u ntreated mice. Autoantibodies to OxCL correlated with aortic isoprostane F- 2 alpha-VI levels(r(2) = 0.42, P = .001 for IgG and r(2) = 0.63, P < .001 f or IgM). Both aortic isoprostane F-2<alpha>-VI levels (r(2) = 0.59, P < .00 1) and titers of OxCL antibodies (r(2) = 0.70, P < .001 for IgG and r(2) = 0.68, P < .001 for IgM) correlated with the extent of aortic atherosclerosi s, The fact that the levels of autoantibodies to OxCL correlated with a sen sitive direct measure of lipid peroxidation in vivo and that both autoantib odies and aortic isoprostane F-2<alpha>-VI levels correlated with the exten t of atherosclerosis suggests that antibodies to OxCL are a sensitive indic ator of in vivo lipid peroxidation and atherosclerosis. (C) 2001 by The Ame rican Society of Hematology.