OXIDIZED LOW-DENSITY-LIPOPROTEIN (OX-LDL) BUT NOT LDL AGGRAVATES THE MANIFESTATIONS OF EXPERIMENTAL ANTIPHOSPHOLIPID SYNDROME (APS)

Ox-LDL is thought to play a major role in atherogenesis. The mechanism s mediating the deleterious influences of Ox-LDL include foam cell for mation and cell cytotoxicity. The production of anti-Ox-LDL antibodies results in the formation of immune complexes which are taken up at en hanced rate by macrophages, leading to foam cell formation. APS is cha racterized by repeated venous and arterial thromboembolic phenomena, r ecurrent fetal loss and thrombocytopenia, associated with the presence of antibodies to negatively charged phospholipids (aPL) (i.e. cardiol ipin, phosphatidylserine). Phospholipids bear structural resemblance t o LDL, and several studies have indeed proved that aPL display cross-r eactivity with anti-Ox-LDL antibodies. In this study we assessed the c apacity of oxidized and native forms of LDL to aggravate the clinical picture of experimentally induced APS in naive mice. Mice were activel y immunized intradermally with anticardiolipin antibodies and develope d a clinical picture resembling APS in humans. Subsequently, the mice were infused with either Ox-LDL, native LDL or PBS, and similar regime ns were applied to controls. APS mice infused with Ox-LDL were found t o exhibit a significantly more severe form of the disease in compariso n with native LDL- and PBS-infused mice, expressed by lower platelet c ounts (261 000/mm(3), 535 000/mm(3) and 455 000/mm(3), respectively), longer activated partial thromboplastin time (aPTT) (99 +/- 12 s, 63 /- s s and 74 +/- 8 s respectively) and higher fetal resorption rates (72.7%, 34.4% and 32.6%, respectively). The results of this study show that Ox-LDL, compared with native LDL, aggravates the clinical manife stations of experimental APS and suggest that cross-reactivity of Ox-L DL with phospholipids may provide a pathogenic explanation for this ef fect.