Liraglutide Ameliorates Injury-Related Vascular Repair by Activating Autophagy Through Modulation of the PI3K-mTOR Signaling Pathway.

Chronic stress is a significant risk factor for postoperative restenosis and other cardiovascular diseases, as it can promote the intimal thickening of damaged vessels. Liraglutide is used primarily for the treatment of type 2 diabetes and obesity. Recently, the protective effects of liraglutide on the cardiovascular system have garnered widespread attention; however, its specific mechanism of action remains unknown. The aim of this study was to investigate the impact of liraglutide on chronic stress-induced thickening of the damaged vascular intima and to elucidate the underlying mechanism involved. A dual in vivo model of chronic stress and carotid intima injury was adopted to investigate the effects of chronic stress on vascular morphology, blood biochemistry, and the expression of autophagy and apoptosis-related proteins in the carotid arteries and liver tissues of mice with vascular injury. We examined the effects of liraglutide on the proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMCs) in vitro. The results revealed that chronic stress increased neointimal formation and upregulated the expression of autophagy-related factors in the injured carotid artery and liver tissues of mice subjected to carotid artery ligation. Liraglutide significantly reversed these changes and suppressed the proliferation, migration, and apoptosis of VSMCs. In summary, chronic stress exacerbates intimal thickening in injured arteries and accelerates the onset of postoperative restenosis. Liraglutide decreased the incidence of postoperative restenosis, potentially by inhibiting the p38MAPK/mTOR signaling pathway, enhancing autophagy, and reducing the abnormal proliferation, migration, and apoptosis of VSMCs.