Reduction of atherosclerosis in low-density lipoprotein receptor-deficient mice by passive administration of antiphospholipid antibody

Objective. Patients with antiphospholipid syndrome (APS) are at a high risk of developing atherosclerotic complications. Conversely, individuals with primary atherosclerosis have an increased prevalence of antiphospholipid antibodies (aPL) and antibodies to oxidized low-density lipoproteins (ox-LDL). Several studies suggest that these two antibody populations may in fact overlap, although it is unclear how aPL contribute to pathogenesis. In this study, we characterized an IgG monoclonal aPL and assessed its ability to modulate atherosclerosis in low-density lipoprotein receptor-deficient (LDLR-/-) mice. Methods. The cardiolipin-reactive monoclonal antibody FBI was obtained from an (NZW X BXSB)F-1 mouse, a strain with APS features that make it prone to fatal myocardial infarctions. Using an enzyme-linked immunosorbent assay, we investigated the binding of this antibody to phospholipid and LDL antigens. We also passively administered FBI to atherosclerosisprone mice to determine its effect on atherogenesis. Results. In contrast to earlier studies of aPL that were specific for oxidized forms of LDL, FBI cross-reacted with both native LDL and ox-LDL. In vivo, passive administration of FBI significantly reduced plaque formation in atherosclerosis-prone LDLR-/- mice. Conclusion. These results indicate that some aPL may play a protective role in atherogenesis and suggest a novel approach to the prevention of atherosclerosis.