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Macrophage deficiency of Akt2 reduces atherosclerosis in Ldlr null mice
Macrophages play crucial roles in the formation of atherosclerotic lesions. Akt, a serine/threonine protein kinase B, is vital for cell proliferation, migration, and survival. Macrophages express three Akt isoforms, Akt1, Akt2, and Akt3, but the roles of Akt1 and Akt2 in atherosclerosis in vivo rema...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Biochemistry and Molecular Biology
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617132/ https://www.ncbi.nlm.nih.gov/pubmed/25240046 http://dx.doi.org/10.1194/jlr.M050633 |
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author | Babaev, Vladimir R. Hebron, Katie E. Wiese, Carrie B. Toth, Cynthia L. Ding, Lei Zhang, Youmin May, James M. Fazio, Sergio Vickers, Kasey C. Linton, MacRae F. |
author_facet | Babaev, Vladimir R. Hebron, Katie E. Wiese, Carrie B. Toth, Cynthia L. Ding, Lei Zhang, Youmin May, James M. Fazio, Sergio Vickers, Kasey C. Linton, MacRae F. |
author_sort | Babaev, Vladimir R. |
collection | PubMed |
description | Macrophages play crucial roles in the formation of atherosclerotic lesions. Akt, a serine/threonine protein kinase B, is vital for cell proliferation, migration, and survival. Macrophages express three Akt isoforms, Akt1, Akt2, and Akt3, but the roles of Akt1 and Akt2 in atherosclerosis in vivo remain unclear. To dissect the impact of macrophage Akt1 and Akt2 on early atherosclerosis, we generated mice with hematopoietic deficiency of Akt1 or Akt2. After 8 weeks on Western diet, Ldlr(−/−) mice reconstituted with Akt1(−/−) fetal liver cells (Akt1(−/−)→Ldlr(−/−)) had similar atherosclerotic lesion areas compared with control mice transplanted with WT cells (WT→Ldlr(−/−)). In contrast, Akt2(−/−)→Ldlr(−/−) mice had dramatically reduced atherosclerotic lesions compared with WT→Ldlr(−/−) mice of both genders. Similarly, in the setting of advanced atherosclerotic lesions, Akt2(−/−)→Ldlr(−/−) mice had smaller aortic lesions compared with WT→Ldlr(−/−) and Akt1(−/−)→Ldlr(−/−) mice. Importantly, Akt2(−/−)→Ldlr(−/−) mice had reduced numbers of proinflammatory blood monocytes expressing Ly-6C(hi) and chemokine C-C motif receptor 2. Peritoneal macrophages isolated from Akt2(−/−) mice were skewed toward an M2 phenotype and showed decreased expression of proinflammatory genes and reduced cell migration. Our data demonstrate that loss of Akt2 suppresses the ability of macrophages to undergo M1 polarization reducing both early and advanced atherosclerosis. |
format | Online Article Text |
id | pubmed-4617132 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-46171322015-10-28 Macrophage deficiency of Akt2 reduces atherosclerosis in Ldlr null mice Babaev, Vladimir R. Hebron, Katie E. Wiese, Carrie B. Toth, Cynthia L. Ding, Lei Zhang, Youmin May, James M. Fazio, Sergio Vickers, Kasey C. Linton, MacRae F. J Lipid Res Research Articles Macrophages play crucial roles in the formation of atherosclerotic lesions. Akt, a serine/threonine protein kinase B, is vital for cell proliferation, migration, and survival. Macrophages express three Akt isoforms, Akt1, Akt2, and Akt3, but the roles of Akt1 and Akt2 in atherosclerosis in vivo remain unclear. To dissect the impact of macrophage Akt1 and Akt2 on early atherosclerosis, we generated mice with hematopoietic deficiency of Akt1 or Akt2. After 8 weeks on Western diet, Ldlr(−/−) mice reconstituted with Akt1(−/−) fetal liver cells (Akt1(−/−)→Ldlr(−/−)) had similar atherosclerotic lesion areas compared with control mice transplanted with WT cells (WT→Ldlr(−/−)). In contrast, Akt2(−/−)→Ldlr(−/−) mice had dramatically reduced atherosclerotic lesions compared with WT→Ldlr(−/−) mice of both genders. Similarly, in the setting of advanced atherosclerotic lesions, Akt2(−/−)→Ldlr(−/−) mice had smaller aortic lesions compared with WT→Ldlr(−/−) and Akt1(−/−)→Ldlr(−/−) mice. Importantly, Akt2(−/−)→Ldlr(−/−) mice had reduced numbers of proinflammatory blood monocytes expressing Ly-6C(hi) and chemokine C-C motif receptor 2. Peritoneal macrophages isolated from Akt2(−/−) mice were skewed toward an M2 phenotype and showed decreased expression of proinflammatory genes and reduced cell migration. Our data demonstrate that loss of Akt2 suppresses the ability of macrophages to undergo M1 polarization reducing both early and advanced atherosclerosis. The American Society for Biochemistry and Molecular Biology 2014-11 /pmc/articles/PMC4617132/ /pubmed/25240046 http://dx.doi.org/10.1194/jlr.M050633 Text en Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc. http://creativecommons.org/licenses/by/3.0/ Author’s Choice—Final version full access. Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/) applies to Author Choice Articles |
spellingShingle | Research Articles Babaev, Vladimir R. Hebron, Katie E. Wiese, Carrie B. Toth, Cynthia L. Ding, Lei Zhang, Youmin May, James M. Fazio, Sergio Vickers, Kasey C. Linton, MacRae F. Macrophage deficiency of Akt2 reduces atherosclerosis in Ldlr null mice |
title | Macrophage deficiency of Akt2 reduces atherosclerosis in Ldlr null mice |
title_full | Macrophage deficiency of Akt2 reduces atherosclerosis in Ldlr null mice |
title_fullStr | Macrophage deficiency of Akt2 reduces atherosclerosis in Ldlr null mice |
title_full_unstemmed | Macrophage deficiency of Akt2 reduces atherosclerosis in Ldlr null mice |
title_short | Macrophage deficiency of Akt2 reduces atherosclerosis in Ldlr null mice |
title_sort | macrophage deficiency of akt2 reduces atherosclerosis in ldlr null mice |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617132/ https://www.ncbi.nlm.nih.gov/pubmed/25240046 http://dx.doi.org/10.1194/jlr.M050633 |
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