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Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms

BACKGROUND AND AIMS: Determine the effect of AMPK activation and inhibition on the development of AAA (abdominal aortic aneurysm). METHODS: AAA was induced in ApoE(−/−) mice by Ang II (Angiotensin II)-infusion. AICAR (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside) was used as AMPK activator an...

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Autores principales: Yang, Le, Shen, Lin, Gao, Peixian, Li, Gang, He, Yuxiang, Wang, Maohua, Zhou, Hua, Yuan, Hai, Jin, Xing, Wu, Xuejun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696225/
https://www.ncbi.nlm.nih.gov/pubmed/29190959
http://dx.doi.org/10.18632/oncotarget.21608
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author Yang, Le
Shen, Lin
Gao, Peixian
Li, Gang
He, Yuxiang
Wang, Maohua
Zhou, Hua
Yuan, Hai
Jin, Xing
Wu, Xuejun
author_facet Yang, Le
Shen, Lin
Gao, Peixian
Li, Gang
He, Yuxiang
Wang, Maohua
Zhou, Hua
Yuan, Hai
Jin, Xing
Wu, Xuejun
author_sort Yang, Le
collection PubMed
description BACKGROUND AND AIMS: Determine the effect of AMPK activation and inhibition on the development of AAA (abdominal aortic aneurysm). METHODS: AAA was induced in ApoE(−/−) mice by Ang II (Angiotensin II)-infusion. AICAR (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside) was used as AMPK activator and Compound C was used as AMPK inhibitor. We further investigate the effect of metformin, a widely used anti-diabetic drug which could activate AMPK signal pathway, on the pathogenesis of aneurysm. RESULTS: Phospho-AMPK level was significantly decreased in AAA tissue compared with control aortas. AICAR significantly reduced the incidence, severity and mortality of aneurysm in the Ang II-infusion model. AICAR also alleviated macrophage infiltration and neovascularity in Ang II infusion model at day 28. The expression of pro-inflammatory factors, angiogenic factors and the activity of MMPs were also alleviated by AICAR during AAA induction. On the other hand, Compound C treatment did not exert obvious protective effect. AMPK activation may inhibit the activation of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription-3 (STAT-3) during AAA induction. Administration of metformin also activated AMPK signal pathway and retarded AAA progression in Ang II infusion model. CONCLUSIONS: Activation of AMPK signaling pathway may inhibit the Ang II-induced AAA in mice. Metformin may be a promising approach to the treatment of AAA.
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spelling pubmed-56962252017-11-29 Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms Yang, Le Shen, Lin Gao, Peixian Li, Gang He, Yuxiang Wang, Maohua Zhou, Hua Yuan, Hai Jin, Xing Wu, Xuejun Oncotarget Research Paper BACKGROUND AND AIMS: Determine the effect of AMPK activation and inhibition on the development of AAA (abdominal aortic aneurysm). METHODS: AAA was induced in ApoE(−/−) mice by Ang II (Angiotensin II)-infusion. AICAR (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside) was used as AMPK activator and Compound C was used as AMPK inhibitor. We further investigate the effect of metformin, a widely used anti-diabetic drug which could activate AMPK signal pathway, on the pathogenesis of aneurysm. RESULTS: Phospho-AMPK level was significantly decreased in AAA tissue compared with control aortas. AICAR significantly reduced the incidence, severity and mortality of aneurysm in the Ang II-infusion model. AICAR also alleviated macrophage infiltration and neovascularity in Ang II infusion model at day 28. The expression of pro-inflammatory factors, angiogenic factors and the activity of MMPs were also alleviated by AICAR during AAA induction. On the other hand, Compound C treatment did not exert obvious protective effect. AMPK activation may inhibit the activation of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription-3 (STAT-3) during AAA induction. Administration of metformin also activated AMPK signal pathway and retarded AAA progression in Ang II infusion model. CONCLUSIONS: Activation of AMPK signaling pathway may inhibit the Ang II-induced AAA in mice. Metformin may be a promising approach to the treatment of AAA. Impact Journals LLC 2017-10-07 /pmc/articles/PMC5696225/ /pubmed/29190959 http://dx.doi.org/10.18632/oncotarget.21608 Text en Copyright: © 2017 Yang et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Yang, Le
Shen, Lin
Gao, Peixian
Li, Gang
He, Yuxiang
Wang, Maohua
Zhou, Hua
Yuan, Hai
Jin, Xing
Wu, Xuejun
Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms
title Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms
title_full Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms
title_fullStr Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms
title_full_unstemmed Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms
title_short Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms
title_sort effect of ampk signal pathway on pathogenesis of abdominal aortic aneurysms
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696225/
https://www.ncbi.nlm.nih.gov/pubmed/29190959
http://dx.doi.org/10.18632/oncotarget.21608
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