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

Lewis, Ruth D., Jackson, Christopher L., Morgan, Bryan Paul and Hughes, Timothy Richard 2010. The membrane attack complex of complement drives the progression of atherosclerosis in apolipoprotein E knockout mice. Molecular Immunology 47 (5) , pp. 1098-1105. 10.1016/j.molimm.2009.10.035

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords: Atherosclerosis; Complement; Membrane attack complex; Apolipoprotein E knockout mouse
Publisher: Elsevier
ISSN: 0161-5890
Last Modified: 07 Sep 2018 21:55
URI: http://orca-mwe.cf.ac.uk/id/eprint/25598

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