Yang Le, Shen Lin, Gao Peixian, Li Gang, He Yuxiang, Wang Maohua, Zhou Hua, Yuan Hai, Jin Xing, Wu Xuejun
Department of Vascular Surgery, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250012, China.
Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan 250012, China.
Oncotarget. 2017 Oct 7;8(54):92827-92840. doi: 10.18632/oncotarget.21608. eCollection 2017 Nov 3.
Determine the effect of AMPK activation and inhibition on the development of AAA (abdominal aortic aneurysm).
AAA was induced in 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.
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.
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.
确定AMPK激活和抑制对腹主动脉瘤（AAA）发展的影响。
通过输注血管紧张素II（Ang II）在小鼠中诱导产生AAA。5-氨基咪唑-4-甲酰胺-1-β-D-呋喃核糖苷（AICAR）用作AMPK激活剂，化合物C用作AMPK抑制剂。我们进一步研究了二甲双胍（一种广泛使用的可激活AMPK信号通路的抗糖尿病药物）对动脉瘤发病机制的影响。
与对照主动脉相比，AAA组织中的磷酸化AMPK水平显著降低。AICAR显著降低了Ang II输注模型中动脉瘤的发生率、严重程度和死亡率。在第28天，AICAR还减轻了Ang II输注模型中的巨噬细胞浸润和新生血管形成。在AAA诱导过程中，AICAR还减轻了促炎因子、血管生成因子的表达以及基质金属蛋白酶的活性。另一方面，化合物C处理未发挥明显的保护作用。在AAA诱导过程中，AMPK激活可能抑制核因子-κB（NF-κB）和信号转导及转录激活因子-3（STAT-3）的激活。给予二甲双胍也激活了AMPK信号通路，并延缓了Ang II输注模型中AAA的进展。
AMPK信号通路的激活可能抑制小鼠中Ang II诱导的AAA。二甲双胍可能是一种有前景的AAA治疗方法。
