Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms

// Le Yang 1 , Lin Shen 2 , Peixian Gao 1 , Gang Li 1 , Yuxiang He 1 , Maohua Wang 1 , Hua Zhou 1 , Hai Yuan 1 , Xing Jin 1 and Xuejun Wu 1 1 Department of Vascular Surgery, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250012, China 2 Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan 250012, China Correspondence to: Xuejun Wu, email: wuxuejun0704@163.com 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.