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-/-).


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.
Persson
Linda
L
Department of Medical Biochemistry,The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
Borén
Jan
J
Robertson
Anna-Karin L
AK
Wallenius
Ville
V
Hansson
Göran K
GK
Pekna
Marcela
M
D000818:Animals; D001018:Aortic Diseases / Q000097:blood / Q000235:genetics* / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008078:Cholesterol, LDL / Q000097:blood; D003176:Complement C3 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D011415:Complement Factor B / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D003170:Complement Pathway, Alternative / Q000235:genetics; D003171:Complement Pathway, Classical / Q000235:genetics; D003433:Crosses, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics; D006953:Hyperlipoproteinemia Type IV / Q000097:blood / Q000235:genetics; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D003176:Complement C3; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D011415:Complement Factor B