on April 1, 2004
Published online before print April 1, 2004, doi: 10.1161/01.ATV.0000127302.24266.40
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Submitted on December 22, 2003
Accepted on March 22, 2004
Lack of Complement Factor C3, but Not Factor B, Increases Hyperlipidemia and Atherosclerosis in Apolipoprotein E-/- Low-Density Lipoprotein Receptor-/- Mice
Linda Persson ;
From the Department of Medical Biochemistry (L.P., M.P.), Wallenberg Laboratory for Cardiovascular Research (J.B.), and Research Center for Endocrinology and Metabolism (V.W.), The Sahlgrenska Academy at Göteborg University, Göteborg; and the Center for Molecular Medicine (G.K.H., A.-K.R.), Karolinska Institute, Stockholm, Sweden
* To whom correspondence should be addressed. E-mail: Marcela.Pekna{at}medkem.gu.se.
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.
Key words: atherosclerosis • complement • C3 • factor B • hyperlipidemia
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