Lipoprotein(a) oxidation and autoantibodies: a new path in atherothrombosis

Lipoprotein(a) (Lp(a)) is considered a vascular pathogen of outstanding imp ortance. High plasma levels of this lipoprotein are associated with prematu re arterial disease; however, the mechanisms involved have not been clarifi ed. The atherosclerotic process is increasingly regarded as a chronic infla mmatory reaction in the arterial wall where oxidation-mediated endothelial injury involving modified forms of low-density lipoprotein (LDL) seems to b e a key event. Autoimmune pathways are involved in the progression of ather osclerosis and humoral response to oxidatively modified LDL can be consider ed among these pathways. A number of factors can be encountered in the pathogenesis of the accelerat ed arterial disease seen in patients with antiphospholipid (Hughes) syndrom e (APS) and systemic lupus crythematosus (SLE). Among these, high levels of Lp(a) have been described in both and increasing evidence indicates that p atients with antiphospholipid antibodies (aPL) are under oxidative stress. Recent studies suggest that the so-called 'oxidation theory of atherosclero sis' may also be applied to Lp(a). This fact makes this lipoprotein potenti ally suitable as a target of the immune system and antibodies reacting agai nst oxidatively-modified Lp(a) by malondialdehyde have been recently descri bed in APS and SLE. It is therefore likely that an immune response to the o xidized moiety of Lp(a) might be influential in the pathogenicity of this l ipoprotein and, subsequently, of atherosclerosis.