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 < 0.00005). The C3-/- mice also had 58% higher serum triglyceride levels (P < 0.05) and a more proatherogenic lipoprotein profile, with significantly more low-density lipoprotein cholesterol and very-low-density lipoprotein triglycerides than control mice. The C3-/- mice weighed 13% less (P < 0.01) and had a lower body fat content (3.5% +/- 1.0% versus 13.1% +/- 3.0%, P < 0.01). There were no differences between FB-/- mice and controls. Conclusions - Complement activation by the classical or lectin pathway exerts atheroprotective effects, possibly through the regulation of lipid metabolism.