Oncotarget

Research Papers:

Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms

Le Yang, Lin Shen, Peixian Gao, Gang Li, Yuxiang He, Maohua Wang, Hua Zhou, Hai Yuan, Xing Jin and Xuejun Wu _

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Oncotarget. 2017; 8:92827-92840. https://doi.org/10.18632/oncotarget.21608

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Abstract

Le Yang1, Lin Shen2, Peixian Gao1, Gang Li1, Yuxiang He1, Maohua Wang1, Hua Zhou1, Hai Yuan1, Xing Jin1 and Xuejun Wu1

1Department of Vascular Surgery, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250012, China

2Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan 250012, China

Correspondence to:

Xuejun Wu, email: [email protected]

Keywords: AMPK, aneurysm, inflammation, neovascularization, MMP

Received: November 18, 2016    Accepted: August 26, 2017    Published: October 07, 2017

ABSTRACT

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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