Complement activation by oxidatively modified low-density lipoproteins.
BACKGROUND
Oxidatively modified low-density lipoproteins (LDLs) have been implicated in the pathogenesis of atherosclerosis and are found in human vascular 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 isolated from lesions have been shown to activate complement, hence their designation as lesion complement activator (LCA). The question now arose whether oxidized LDLs would also activate complement.


METHODS
The complement-activating capacity of a lesion complement activator preparation and of minimally as well as heavily oxidized LDL was investigated by measuring SC5b-9 formation in normal human serum. In addition, C3 conversion was followed using two-dimensional immunoelectrophoresis.


RESULTS
Minimally and heavily oxidized LDL generated small but significant amounts of SC5b-9 (7.9 microgram mL-1, SD 3.5, and 10.8 microgram mL-1, SD 1.2, respectively; n = 6) compared with native LDL (3.3 microgram mL-1, SD 1.4; P < 0.05), whereas LCA generated substantially larger amounts of the terminal complex (32.0 microgram mL-1, SD 3.2). Both oxidized LDL preparations caused only minor C3 conversion.


CONCLUSIONS
These findings show that oxidation does not confer relevant complement-activating properties on LDL, suggesting that the lesion complement activator is not directly related to oxidized LDL. Oxidized LDL is probably of minor importance for complement activation in atherosclerotic lesions.
Wieland
E
E
Georg-August-Universität, Göttingen, Germany. ewieland@med.uni-goettingen.de
Dorweiler
B
B
Bonitz
U
U
Lieser
S
S
Walev
I
I
Bhakdi
S
S
D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D010084:Oxidation-Reduction
D003176:Complement C3; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D008315:Malondialdehyde; D002784:Cholesterol