Lipoprotein(a) oxidation and autoantibodies: a new path in atherothrombosis.
Lipoprotein(a) (Lp(a)) is considered a vascular pathogen of outstanding importance. High plasma levels of this lipoprotein are associated with premature arterial disease; however, the mechanisms involved have not been clarified. The atherosclerotic process is increasingly regarded as a chronic inflammatory reaction in the arterial wall where oxidation-mediated endothelial injury involving modified forms of low-density lipoprotein (LDL) seems to be a key event. Autoimmune pathways are involved in the progression of atherosclerosis and humoral response to oxidatively modified LDL can be considered among these pathways. A number of factors can be encountered in the pathogenesis of the accelerated arterial disease seen in patients with antiphospholipid (Hughes) syndrome (APS) and systemic lupus erythematosus (SLE). Among these, high levels of Lp(a) have been described in both and increasing evidence indicates that patients with antiphospholipid antibodies (aPL) are under oxidative stress. Recent studies suggest that the so-called 'oxidation theory of atherosclerosis' may also be applied to Lp(a). This fact makes this lipoprotein potentially suitable as a target of the immune system and antibodies reacting against oxidatively-modified Lp(a) by malondialdehyde have been recently described in APS and SLE. It is therefore likely that an immune response to the oxidized moiety of Lp(a) might be influential in the pathogenicity of this lipoprotein and, subsequently, of atherosclerosis.
Romero
F I
FI
Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, London, UK.
Khamashta
M A
MA
Hughes
G R
GR
D016736:Antiphospholipid Syndrome / Q000150:complications / Q000276:immunology; D001161:Arteriosclerosis / Q000209:etiology* / Q000276:immunology*; D001323:Autoantibodies / Q000378:metabolism*; D006801:Humans; D017270:Lipoprotein(a) / Q000276:immunology* / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000276:immunology; D008315:Malondialdehyde / Q000378:metabolism; D010084:Oxidation-Reduction
D001323:Autoantibodies; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D008315:Malondialdehyde