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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aortic Diseases / blood
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Aortic Diseases / genetics*
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Aortic Diseases / pathology
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Apolipoproteins E / deficiency
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Apolipoproteins E / genetics
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Arteriosclerosis / blood
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Arteriosclerosis / genetics*
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Arteriosclerosis / pathology
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Cholesterol, LDL / blood
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Complement C3 / deficiency*
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Complement C3 / genetics
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Complement C3 / physiology
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Complement Factor B / deficiency*
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Complement Factor B / genetics
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Complement Factor B / physiology
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Complement Pathway, Alternative / genetics
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Complement Pathway, Classical / genetics
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Crosses, Genetic
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Female
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Genetic Predisposition to Disease
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Hyperlipoproteinemia Type II / blood
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Hyperlipoproteinemia Type II / genetics
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Hyperlipoproteinemia Type IV / blood
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Hyperlipoproteinemia Type IV / genetics
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Lipoproteins, VLDL / blood
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Male
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Mice
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Mice, Knockout
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Receptors, LDL / deficiency
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Receptors, LDL / genetics
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Triglycerides / blood
Substances
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Apolipoproteins E
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Cholesterol, LDL
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Complement C3
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Lipoproteins, VLDL
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Receptors, LDL
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Triglycerides
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very low density lipoprotein triglyceride
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Complement Factor B