ISSN : 2146-3123
E-ISSN : 2146-3131

The Key Role of Liraglutide in Preventing Autophagy of Vascular Smooth Muscle Cells in High Glucose Conditions
Lili Shi1, Ming Hao2, Guangjing Qu1, Yingying Xu1, Zhe Cui1, Lin Geng1, Hongyu Kuang2
1Department of Cadre ward, The First Affiliated Hospital of Harbin Medical University, Harbin, China
2Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University,Harbin, China
DOI : 10.4274/balkanmedj.galenos.2023.2023-8-44

Background: The glucagon-like peptide-1 (GLP-1) receptor agonistliraglutide (LIRA) is a potential hypoglycemic drug with antiatherosclerosis(AS) effects. Autophagy in the vascular smooth musclecells (VSMCs) facilitates AS. However, the role of autophagy in theanti-AS mechanism of LIRA remains unclear.
Aims: To examine the role and mechanisms of autophagy in LIRA’simprovement of the biological characteristics of VSMCs in highglucose conditions.
Study Design: A VSMC injury model induced by high glucoseconcentrations was used to detect the regulatory effects of LIRAon VSMC autophagy, calcification, migration, proliferation andphenotype conversion.
Methods: VSMCs isolated from the thoracic aorta of male SDrats were subjected to a high glucose (HG) condition (25 mM) inDulbecco’s Modified Eagle’s Medium with or without LIRA, the GLP-1 receptor antagonist exendin9-39 (Exe9-39), a phosphatidylinositol3-kinase (PI3K) inhibitor (LY294002), and autophagy inhibitors(3-methyladenine [3-MA] and bafilomycin A1 [Baf A1]). Acridineorange staining, western blotting, transmission electron microscopy,and mCherry-GFP-LC3 transfection were performed to evaluatethe autophagy flux. Additionally, VSMC migration, calcification,proliferation, and apoptosis in HG conditions were observed.Results: Addition of LIRA alone or in combination with autophagyinhibitors significantly downregulated Beclin, increased the LC3-II/LC3-I ratio, and upregulated p62 in VSMCs in HG conditions.Furthermore, autophagolysosome formation was markedly curbedafter treatment with LIRA and/or autophagy inhibitors. Inhibition ofautophagy by LIRA and/or the autophagy inhibitors attenuated VSMCphenotype conversion, proliferation, migration, and calcification andpromoted VSMC apoptosis in HG conditions. This protective role ofLIRA was augmented by LY294002, but inhibited by Exe9-39.Conclusion: LIRA plays a significant role in the improvement of thebiological features of VSMCs in HG conditions.

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