HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Circulating autoantibodies to oxidized cardiolipin correlate with isoprostane F2a-VI levels and the extent of atherosclerosis in ApoE-deficient mice: modulation by vitamin E

Lipid peroxidation plays an important role in atherogenesis. Previous studies suggested that autoantibodies against epitopes of oxidized low-density lipoprotein may indicate the extent or rate of progression of atherosclerosis. The aim of this study was to investigate whether autoantibodies to oxidized phospholipids, such as oxidized cardiolipin (OxCL), correlate with levels of isoprostane F2a-VI, a sensitive marker of in vivo lipid peroxidation, as well as with the extent of atherosclerosis. Two groups of apolipoprotein E-deficient mice were fed chow with or without vitamin E (2000 IU/kg diet) for 16 weeks. In untreated animals, autoantibodies against OxCL and urinary, plasma, and aortic isoprostane F2a-VI levels increased significantly. Vitamin E treatment significantly reduced antibody titers, isoprostane levels, and atherosclerosis at the end of the study, compared with untreated mice. Autoantibodies to OxCL correlated with aortic isoprostane F2a-VI levels (r 2 5 0.42, P 5 .001 for IgG and r 2 5 0.63, P < .001 for IgM). Both aortic isoprostane F2a-VI levels (r 2 5 0.59, P < .001) and titers of OxCL antibodies (r 2 5 0.70, P < .001 for IgG and r 2 5 0.68, P < .001 for IgM) correlated with the extent of aortic atherosclerosis. The fact that the levels of autoantibodies to OxCL correlated with a sensitive direct measure of lipid peroxidation in vivo and that both autoantibodies and aortic isoprostane F2a-VI levels correlated with the extent of atherosclerosis suggests that antibodies to OxCL are a sensitive indicator of in vivo lipid peroxidation and atherosclerosis. (Blood. 2001; 97:459-464)