Lack of complement factor C3, but not factor B, increases hyperlipidemia and atherosclerosis in apolipoprotein E-/- low-density lipoprotein receptor-/- mice.

Abstract

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.

• Authors: Linda Persson, Jan Borén, Anna-Karin L Robertson, Ville Wallenius, Göran K Hansson, Marcela Pekna
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 24 Issue 6 Pg. 1062-7 (Jun 2004) ISSN: 1524-4636 [Electronic] United States
• PMID: 15059809 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• Cholesterol, LDL
• Complement C3
• Lipoproteins, VLDL
• Receptors, LDL
• Triglycerides
• very low density lipoprotein triglyceride
• Complement Factor B

Topics

• Animals
• Aortic Diseases (blood, genetics, pathology)
• Apolipoproteins E (deficiency, genetics)
• Arteriosclerosis (blood, genetics, pathology)
• Cholesterol, LDL (blood)
• 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
• Hyperlipoproteinemia Type II (blood, genetics)
• Hyperlipoproteinemia Type IV (blood, genetics)
• Lipoproteins, VLDL (blood)
• Male
• Mice
• Mice, Knockout
• Receptors, LDL (deficiency, genetics)
• Triglycerides (blood)