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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1062.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

Linda Persson; Jan Borén; Anna-Karin L. Robertson; Ville Wallenius; Göran K. Hansson; Marcela Pekna

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 (A.-K.L.R., G.K.H.), Karolinska Institute, Stockholm, Sweden

Correspondence to Dr Marcela Pekna, Department of Medical Biochemistry, Göteborg University Box 440 S-405 30, Göteborg, Sweden. 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.

Deficiency in C3, but not in factor B, leads to more extensive atherosclerotic lesions, increased hyperlipidemia, and reduced body fat in Apoe–/– LDLR–/– mice. 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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