Atg7 Mediates Metformin Protected Abdominal Aortic Aneurysm by Inducing Autophagy

Abstract

BackgroundAbdominal aortic aneurysm (AAA) is pathologic dilation of the abdominal aorta and is often asymptomatic but has high susceptibility to rupture. Our previous study showed that metformin protected the pathophysiology of AAA by reducing the activation of PI3K/AKT/mTOR pathway. MethodsAngiotensin II (Ang-II) was used to construct the AAA model in vascular smooth muscle cells (VSMCs). The expression of Atg7 and Atg4 was determined by qRT-PCR and Western blot. Atg7 expression was regulated by overexpressed plasmid or siRNA to examine the cell proliferation, cell migration, cell apoptosis and autophagy caused by Ang-II. ResultsAng-II induced the expression of Atg7 and metformin reversed this effect. Suppression of Atg7 inhibited cell proliferation and cell migration, reduced cell apoptosis and autophagy, while overexpression of Atg7 enhanced cell proliferation and cell migration, induced cell apoptosis and autophagy. Moreover, the expression of autophagy related protein was regulated by Atg7 in Ang-II treated VSMCs. We further showed that the Atg7 mediated-autophagy was attenuated by metformin. ConclusionMetformin-reduced autophagy in AAA was mediated by Atg7, suggesting that Atg7 was a potential downstream effector of metformin in protecting the pathophysiology of AAA.