ApoE super(-/-) Mice Develop Atherosclerosis in the Absence of Complement Component C5

Previous studies have suggested that the terminal complex of complement may contribute to the pathogenesis of atherosclerosis. C5b-9 complexes colocalize with the extracellular lipid in the aortic intima of hypercholesterolemic rabbits, and C6-deficient rabbits develop less atherosclerosis than controls. To test the role of complement in atherosclerosis in a different animal model, C5 deficient (C5def) mice were cross-bred with atherosclerosis susceptible apoE super(-/-) mice, generating mice deficient in both apoE and C5 and control apoE super(-/-) mice. Progeny were typed for C5 titer and serum cholesterol levels. Both male and female mice were fed a high fat diet from weaning until 22 weeks of age. At that time there were no significant differences in plasma cholesterol or triglycerides between apoE super(-/-) control and apoE super(-/-)/C5def groups. Morphometric analysis of the aortic root lesions gave mean ( plus or minus SEM) lesion areas for male apoE super(-/-) and apoE super(-/-)/C5def mice of 468,176 plus or minus 21,982 and 375,182 plus or minus 53,089 mu m super(2), respectively (n = 10 each, P value = 0.123). In female apoE super(-/-) mice (n = 5), the mean lesion area was 591,981 plus or minus 53,242 mu m super(2), compared to 618,578 plus or minus 83,457 mu m super(2) for female apoE super(-/-)/C5def mice (n = 10) (P value = 0.835). Thus neither male nor female mice showed a significant change in lesion area when C5 was not present. In contrast to the case in the hypercholesterolemic rabbit, activation of the terminal complex of complement does not play a major role in the development of atherosclerosis in apoE super(-/-) mice. Copyright 2001 Academic Press.