Lack of Complement Factor C3, but Not Factor B, Increases Hyperlipidemia and Atherosclerosis in Apolipoprotein E-/- Low-Density Lipoprotein Receptor-/- Mice

Objective— To investigate the effect of complement deficiency on atherogenesis and lipidemia, we used mice deficient in the third complement component ( C3 −/−) or factor B ( FB −/−). Methods and Results— Complement-deficient mice were crossed with mice deficient in both apolipoprotein E and the low-density lipoprotein receptor ( Apoe −/− LDLR −/−). The percent lesion area in the aorta at 16 weeks, determined by en face analysis, was 84% higher in C3 −/− mice than in controls (11.8%±0.4% versus 6.4%±0.8%, mean±SEM, P C3 −/− mice also had 58% higher serum triglyceride levels ( P C3 −/− mice weighed 13% less ( P P FB −/− mice and controls. Conclusions— Complement activation by the classical or lectin pathway exerts atheroprotective effects, possibly through the regulation of lipid metabolism.