Abstract
Abdominal aortic aneurysm (AAA) is a pathological dilation of the abdominal aorta. It is often asymptomatic, yet it has a high susceptibility to rupture. Our previous study showed that metformin protected against the pathophysiology of AAA by reducing the activation of the PI3K/AKT/mTOR pathway. To investigate the potential involvement of the autophagy-related pathways in AAA and the ability of metformin to modulate these effects. The expression of autophagy-related proteins was detected with western blot in patients with AAA. Angiotensin II (Ang-II) was also used to construct an AAA model in mice and in vascular smooth muscle cells (VSMCs). The expression of Atg7 and Atg4 was determined using western blot assay. The Atg7 expression was regulated by overexpressed plasmid, siRNA (small interfering RNA), or metformin, and cell proliferation, migration, apoptosis and autophagy caused by Ang-II were examined. Autophagy-related proteins were increased in patients with AAA. The Ang-II also induced the expression of Atg7, and metformin reversed this effect both in vivo and in vitro. The suppression of Atg7 inhibited cell proliferation and cell migration, and reduced cell apoptosis and autophagy, while the overexpression of Atg7 enhanced cell proliferation and migration, and induced cell apoptosis and autophagy. Furthermore, Atg7 regulated the expression of the autophagy-related protein in Ang-II treated VSMCs. The Atg7-mediated autophagy was also attenuated by metformin. Metformin reduced autophagy in AAA and this effect was mediated by Atg7, suggesting that Atg7 is a potential downstream effector of metformin in protecting against the pathophysiology of AAA.
Highlights
Abdominal aortic aneurysm (AAA) is a pathological dilation of the abdominal aorta
Metformin reduced autophagy in AAA and this effect was mediated by Autophagyrelated genes (Atgs)[7], suggesting that Atg[7] is a potential downstream effector of metformin in protecting against the pathophysiology of AAA
The Angiotensin II (Ang-II) was used to construct a mouse AAA model, and it was discovered that AngII induced the expression levels of Atg[7], Beclin 1 and LC3B II/I, and reduced the expression of p62 (Fig. 2B)
Summary
Abdominal aortic aneurysm (AAA) is a pathological dilation of the abdominal aorta. It is often asymptomatic, yet it has a high susceptibility to rupture. Abdominal aortic aneurysm (AAA), a degenerative vascular disease, is a pathological dilation that can lead to a potentially fatal aortic rupture.[1] the incidence of AAA has recently decreased,[2] the worldwide mortality rate due to this condition has remained stable.[3] Aneurysms are characterized by a decrease in the number of medial smooth muscle cells (SMCs) in the aortic wall.[1] An increasing number of studies have reported that the development of AAA is associated with a reduction in the structural integrity of the vessel wall, which is caused by cell apoptosis and senescence in SMCs.[4,5] While the histopathological features of AAA are well documented, the cellular and molecular mechanisms underlying the pathogenesis of AAA remain unclear, and no effective pharmacological therapy has been identified to prevent AAA. The search for a novel therapeutic approach remains a challenge
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