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 amoun ts of lipids. Recently, it has been shown that the immune system plays an active part in the progression of the atherosclerotic plaque altho ugh its precise role has not yet been elucidated. Anticardiolipin anti bodies (aCL) are generally found in the sera of patients with the anti phospholipid syndrome (APS) and are associated with a prothrombotic st ate. Several authors have demonstrated that aCL can activate platelets and endothelial cells as well as increase oxidized low density lipopr otein (LDL) uptake by macrophages. In the present study we sought to a ssess the effect of immunization with aCL (Ab1, leading to the product ion of mouse aCL-Ab3) on the progression of atherosclerosis. Two group s 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 w ith normal human IgG, respectively. The aCL immunized mice developed h igh titres of 'self' aCL (detected using the standard aCL ELISA) as co mpared with the normal human IgG immunized mice, whereas no difference s 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 m ice (mean aortic lesion size of 5308 +/- 471 mu m(2) vs 1027 +/- 184 m u m(2), respectively, P < 0.01). The immunohistochemical analysis of t he atherosclerotic plaques from both mouse groups did not display diff erences in cellular composition. The results of the study show that mo use aCL induced by immunization with human aCL from an APS patient enh ance atherogenesis in LDL-RKO mice and imply that these antibodies may play a role in atherosclerosis development in patients with the APS.