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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 knocko...

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Detalles Bibliográficos
Autores principales: Lewis, Ruth D., Jackson, Christopher L., Morgan, B. Paul, Hughes, Timothy R.
Formato: Texto
Lenguaje:English
Publicado: Pergamon Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862291/
https://www.ncbi.nlm.nih.gov/pubmed/19959238
http://dx.doi.org/10.1016/j.molimm.2009.10.035
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author Lewis, Ruth D.
Jackson, Christopher L.
Morgan, B. Paul
Hughes, Timothy R.
author_facet Lewis, Ruth D.
Jackson, Christopher L.
Morgan, B. Paul
Hughes, Timothy R.
author_sort Lewis, Ruth D.
collection PubMed
description 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.
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spelling pubmed-28622912010-05-25 The membrane attack complex of complement drives the progression of atherosclerosis in apolipoprotein E knockout mice Lewis, Ruth D. Jackson, Christopher L. Morgan, B. Paul Hughes, Timothy R. Mol Immunol Article 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. Pergamon Press 2010-02 /pmc/articles/PMC2862291/ /pubmed/19959238 http://dx.doi.org/10.1016/j.molimm.2009.10.035 Text en © 2010 Elsevier Ltd. https://creativecommons.org/licenses/by-nc-nd/3.0/ Open Access under CC BY-NC-ND 3.0 (https://creativecommons.org/licenses/by-nc-nd/3.0/) license
spellingShingle Article
Lewis, Ruth D.
Jackson, Christopher L.
Morgan, B. Paul
Hughes, Timothy R.
The membrane attack complex of complement drives the progression of atherosclerosis in apolipoprotein E knockout mice
title The membrane attack complex of complement drives the progression of atherosclerosis in apolipoprotein E knockout mice
title_full The membrane attack complex of complement drives the progression of atherosclerosis in apolipoprotein E knockout mice
title_fullStr The membrane attack complex of complement drives the progression of atherosclerosis in apolipoprotein E knockout mice
title_full_unstemmed The membrane attack complex of complement drives the progression of atherosclerosis in apolipoprotein E knockout mice
title_short The membrane attack complex of complement drives the progression of atherosclerosis in apolipoprotein E knockout mice
title_sort membrane attack complex of complement drives the progression of atherosclerosis in apolipoprotein e knockout mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862291/
https://www.ncbi.nlm.nih.gov/pubmed/19959238
http://dx.doi.org/10.1016/j.molimm.2009.10.035
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