The membrane attack complex of complement drives the progression of atherosclerosis in apolipoprotein E knockout mice

AIMS: To examine the roles of the membrane attack complex of complement and its sole membrane regulator, CD59, in atherosclerosis. METHODS: C6 (C6(−/−)) deficient and CD59a (Cd59a(−/−)) knockout mice were separately crossed onto the apolipoprotein E knockout (apoE(−/−)) background. The double knockout mice were fed high-fat diet in order to study the effects of absence of C6 or CD59a on the progression of atherosclerosis. RESULTS: C6 deficiency significantly reduced plaque area and disease severity. CD59a had the opposite effect in that deficiency was associated with a significant increase in plaque area, correlating with increased membrane attack complex (MAC) deposition in the plaque and increased smooth muscle cell proliferation in early plaques. CONCLUSIONS: Our results demonstrate that the MAC contributes to the development of atherosclerosis, C6 deficiency being protective and CD59a deficiency exacerbating disease.