Autoimmune-mediated atherothrombosis

Autoimmune vascular inflammation and oxidative stress (lipid peroxidation) are common in systemic autoimmune diseases and contribute to the oxidative modification of low-density lipoprotein (oxLDL) and oxLDL/β2GPI complex formation. Circulating oxLDL/β2GPI complexes have been detected in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). The presence of antibodies to oxLDL/β2GPI complexes indicates that these complexes are immunogenic, and the coexistence of complexes and antibodies has pointed to an active proatherogenic role in the development of autoimmune vascular complications. Immunohistochemical staining of atherosclerotic lesions suggest that these complexes are formed in the arterial wall and released into circulation. The in vitro macrophage uptake of oxLDL/β2GPI complexes was significantly increased in the presence of antiphospholipid antibodies, either β2GPI-dependent anticardiolipin or anti-β2GPI antibodies, suggesting that macrophage Fcγ receptors are involved in lipid intracellular influx and foam cell formation. These findings provide an explanation for the accelerated development of atherosclerosis seen in SLE and APS. The presence of circulating oxLDL/β2GPI complexes and IgG antibodies to these complexes indicate significant vascular injury and oxidative stress as well as an active role in autoimmune-mediated atherothrombosis.

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