Atherosclerosis in LDL-receptor knockout mice is accelerated by immunization with anticardiolipin antibodies.

Atherosclerosis is a process initiated by accumulation of macrophages in distinct areas of endothelial cell damage and uptake of large amounts of lipids. Recently, it has been shown that the immune system plays an active part in the progression of the atherosclerotic plaque although its precise role has not yet been elucidated. Anticardiolipin antibodies (aCL) are generally found in the sera of patients with the antiphospholipid syndrome (APS) and are associated with a prothrombotic state. Several authors have demonstrated that aCL can activate platelets and endothelial cells as well as increase oxidized low density lipoprotein (LDL) uptake by macrophages. In the present study we sought to assess the effect of immunization with aCL (Ab1, leading to the production of mouse aCL-Ab3) on the progression of atherosclerosis. Two groups of 8-weeks old female LDL-receptor knockout mice (n = 13 per group) were immunized with IgG purified from the serum of an APS patient or with normal human IgG, respectively. The aCL immunized mice developed high titres of 'self' aCL (detected using the standard aCL ELISA) as compared with the normal human IgG immunized mice, whereas no differences were noted between both study groups with respect to the serum lipid levels. The extent of fatty streak formation was significantly higher in the aCL immunized mice in comparison with the human IgG injected mice (mean aortic lesion size of 5308 +/- 471 microns2 vs 1027 +/- 184 microns2, respectively, P < 0.01). The immunohistochemical analysis of the atherosclerotic plaques from both mouse groups did not display differences in cellular composition. The results of the study show that mouse aCL induced by immunization with human aCL from an APS patient enhance atherogenesis in LDL-RKO mice and imply that these antibodies may play a role in atherosclerosis development in patients with the APS.