The membrane attack complex of complement drives the progression of atherosclerosis in apolipoprotein E knockout mice.
OBJECTIVE
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.
Lewis
Ruth D
RD
Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Cardiff, UK.
Jackson
Christopher L
CL
Morgan
B Paul
BP
Hughes
Timothy R
TR
D000818:Animals; D001057:Apolipoproteins E; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018957:CD59 Antigens / Q000235:genetics / Q000276:immunology*; D003183:Complement C6 / Q000235:genetics / Q000276:immunology*; D015938:Complement Membrane Attack Complex / Q000235:genetics / Q000276:immunology*; D003433:Crosses, Genetic; D006801:Humans; D051379:Mice; D018345:Mice, Knockout
D001057:Apolipoproteins E; D018957:CD59 Antigens; C539311:CD59a protein, mouse; D003183:Complement C6; D015938:Complement Membrane Attack Complex