Lili Shi, Ming Hao, Guangjing Qu, Yingying Xu, Zhe Cui, Lin Geng, Hongyu Kuang
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引用次数: 0
Abstract
Background: The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (LIRA) is a potential hypoglycemic drug with anti-atherosclerosis (AS) effects. Autophagy in the vascular smooth muscle cells (VSMCs) facilitates AS. However, the role of autophagy in the anti-AS mechanism of LIRA remains unclear.
Aims: To examine the role and mechanisms of autophagy in LIRA’s improvement of the biological characteristics of VSMCs in high glucose conditions.
Study design: Experimental animal study.
Methods: VSMCs isolated from the thoracic aorta of male SD rats were subjected to a high glucose (HG) condition (25 mM) in Dulbecco’s Modified Eagle’s Medium with or without LIRA, the GLP-1 receptor antagonist exendin9-39 (Exe9-39), a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002), and autophagy inhibitors (3-methyladenine [3-MA] and bafilomycin A1 [Baf A1]). Acridine orange staining, western blotting, transmission electron microscopy, and mCherry-GFP-LC3 transfection were performed to evaluate the autophagy flux. Additionally, VSMC migration, calcification, proliferation, and apoptosis in HG conditions were observed.
Results: Addition of LIRA alone or in combination with autophagy inhibitors significantly downregulated Beclin, increased the LC3-II/LC3-I ratio, and upregulated p62 in VSMCs in HG conditions. Furthermore, autophagolysosome formation was markedly curbed after treatment with LIRA and/or autophagy inhibitors. Inhibition of autophagy by LIRA and/or the autophagy inhibitors attenuated VSMC phenotype conversion, proliferation, migration, and calcification and promoted VSMC apoptosis in HG conditions. This protective role of LIRA was augmented by LY294002, but inhibited by Exe9-39.
Conclusion: LIRA plays a significant role in the improvement of the biological features of VSMCs in HG conditions.
期刊介绍:
The Balkan Medical Journal (Balkan Med J) is a peer-reviewed open-access international journal that publishes interesting clinical and experimental research conducted in all fields of medicine, interesting case reports and clinical images, invited reviews, editorials, letters, comments and letters to the Editor including reports on publication and research ethics. The journal is the official scientific publication of the Trakya University Faculty of Medicine, Edirne, Turkey and is printed six times a year, in January, March, May, July, September and November. The language of the journal is English.
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