ApoE−/− Mice Develop Atherosclerosis in the Absence of Complement Component C5

Abstract

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−/− mice, generating mice deficient in both apoE and C5 and control apoE−/− 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−/− control and apoE−/−/C5def groups. Morphometric analysis of the aortic root lesions gave mean (±SEM) lesion areas for male apoE−/− and apoE−/−/C5def mice of 468,176 ± 21,982 and 375,182 ± 53,089 μm2, respectively (n = 10 each, P value = 0.123). In female apoE−/− mice (n = 5), the mean lesion area was 591,981 ± 53,242 μm2, compared to 618,578 ± 83,457 μm2 for female apoE−/−/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−/− mice.