Complement activation by oxidatively modified low-density lipoproteins

Background Oxidatively modified low-density lipoproteins (LDLs) have been i mplicated in the pathogenesis of atherosclerosis and are found in human vas cular lesions. There is increasing evidence that complement activation may also play a role in atherogenesis. Activated complement proteins have been demonstrated to be present in early atherosclerotic lesions, and lipids iso lated from lesions have been shown to activate complement, hence their desi gnation as lesion complement activator (LCA). The question now arose whethe r oxidized LDLs would also activate complement. Material and methods The complement-activating capacity of a lesion complem ent activator preparation and of minimally as well as heavily oxidized LDL was investigated by measuring SC5b-9 formation in normal human serum. In ad dition, C3 conversion was followed using two-dimensional immunoelectrophore sis. Results Minimally and heavily oxidized LDL generated small but significant amounts of SC5b-9 (7.9 mu g mL(-1), SD 3.5, and 10.8 mu g mL(-1), SD 1.2, r espectively; n = 6) compared with native LDL (3.3 mu g mL(-1), SD 1.4; P< 0 .05), whereas LCA generated substantially larger amounts of the terminal co mplex (32.0 mu g mL(-1), SD 3.2). Both oxidized LDL preparations caused onl y minor C3 conversion. Conclusions These findings show that oxidation does not confer relevant com plement-activating properties on LDL, suggesting that the lesion complement activator is not directly related to oxidized LDL. Oxidized LDL is probabl y of minor importance for complement activation in atherosclerotic lesions.