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.

Nyckelord

Animals

Aortic Diseases/blood/ genetics/pathology

Apolipoproteins E/deficiency/genetics

Arteriosclerosis/blood/ genetics/pathology

Comparative Study

Complement C3/ deficiency/genetics/physiology

Complement Factor B/ deficiency/genetics/physiology

Complement Pathway

Alternative/genetics

Complement Pathway

Classical/genetics

Crosses

Genetic

Female

Genetic Predisposition to Disease

Hypercholesterolemia

Familial/blood/genetics

Hyperlipoproteinemia Type IV/blood/genetics

Lipoproteins

LDL Cholesterol/blood

Lipoproteins

VLDL/blood

Male

Mice

Mice

Knockout

Receptors

LDL/deficiency/genetics

Research Support

Non-U.S. Gov't

Triglycerides/blood

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