Metformin protects against abdominal aortic aneurysm by Atg7-induced autophagy
| Autor: | Zhu Wang, Jian Wu, Xinqiang Han, Lei Mi, Mengpeng Zhao, Chao Ma, Jingjing Guo, Ming Xue |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Small interfering RNA
Myocytes Smooth Muscle Medicine (miscellaneous) Autophagy-Related Protein 7 Muscle Smooth Vascular General Biochemistry Genetics and Molecular Biology Mice Phosphatidylinositol 3-Kinases Autophagy Internal Medicine Animals Humans Medicine Pharmacology (medical) Aorta Abdominal Protein kinase B Genetics (clinical) PI3K/AKT/mTOR pathway business.industry Cell growth Angiotensin II Metformin Disease Models Animal Apoptosis Reviews and References (medical) cardiovascular system Cancer research business Aortic Aneurysm Abdominal medicine.drug |
| Zdroj: | Advances in Clinical and Experimental Medicine. 31:59-69 |
| ISSN: | 1899-5276 |
| DOI: | 10.17219/acem/142026 |
| Popis: | Background 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. Objectives To investigate the potential involvement of the autophagy-related pathways in AAA and the ability of metformin to modulate these effects. Material and methods 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. Results 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. Conclusions 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. |
| Databáze: | OpenAIRE |
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