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

Mol Immunol. 2010 Feb;47(5):1098-105. doi: 10.1016/j.molimm.2009.10.035. Epub 2009 Dec 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E*
  • Atherosclerosis / genetics
  • Atherosclerosis / immunology*
  • Atherosclerosis / pathology
  • CD59 Antigens / genetics
  • CD59 Antigens / immunology*
  • Complement C6 / genetics
  • Complement C6 / immunology*
  • Complement Membrane Attack Complex / genetics
  • Complement Membrane Attack Complex / immunology*
  • Crosses, Genetic
  • Humans
  • Mice
  • Mice, Knockout


  • Apolipoproteins E
  • CD59 Antigens
  • CD59a protein, mouse
  • Complement C6
  • Complement Membrane Attack Complex