Dapagliflozin improves the dysfunction of human umbilical vein endothelial cells (HUVECs) by downregulating high glucose/high fat-induced autophagy through inhibiting SGLT-2.

Autor: Lin L; Department of Endocrinology The Second Affiliated Hospital of the University of South China, Hengyang, Hunan 421001, China; Changde Hospital, Xiangya School of Medicine, Central South University (The first people's hospital of Changde city), Changde, Hunan 415000, China., Zhong S; Department of Endocrinology The Second Affiliated Hospital of the University of South China, Hengyang, Hunan 421001, China., Zhou Y; Department of Endocrinology The Second Affiliated Hospital of the University of South China, Hengyang, Hunan 421001, China., Xia J; Department of Endocrinology The Second Affiliated Hospital of the University of South China, Hengyang, Hunan 421001, China., Deng S; Department of Endocrinology The Second Affiliated Hospital of the University of South China, Hengyang, Hunan 421001, China., Jiang T; Department of Endocrinology The Second Affiliated Hospital of the University of South China, Hengyang, Hunan 421001, China., Jiang A; Department of Endocrinology The Second Affiliated Hospital of the University of South China, Hengyang, Hunan 421001, China. Electronic address: 13619095@qq.com., Huang Z; Department of Endocrinology The Second Affiliated Hospital of the University of South China, Hengyang, Hunan 421001, China., Wang J; Department of Endocrinology The Second Affiliated Hospital of the University of South China, Hengyang, Hunan 421001, China. Electronic address: wangjpppp@126.com.
Jazyk: angličtina
Zdroj: Journal of diabetes and its complications [J Diabetes Complications] 2025 Jan; Vol. 39 (1), pp. 108907. Date of Electronic Publication: 2024 Nov 19.
DOI: 10.1016/j.jdiacomp.2024.108907
Abstrakt: Objective: To investigate the effect of Dapagliflozin (Da) on the disorders of human umbilical vein endothelial cells (HUVECs) induced by high glucose and high fat (HG/HF).
Methods: Immunohistochemistry and immunofluorescence were used to detect the SGLT-2 expression in thoracic aortic tissues. After transfected with overexpressed plasmid SLC5A2, autophagy and cell functions of HUVECs were detected with the treatment of autophagy inhibitor 3-MA (5 mM). HUVECs were exposed to mannitol (MAN), glucose/palmitate (Hg/PA), and Hg/PA/Da for 24 h, and the proliferation of HUVECs was detected by CCK-8. The protein expression levels, endothelial cell functions (cell proliferation, migration, tubular formation, apoptosis, and autophagy) in endothelial cells were evaluated.
Results: The SGLT-2 expression was found in atherosclerotic human thoracic aorta tissues and HG/PA induced HUVECs (P < 0.05). After the overexpression of SGLT-2 in HUVECs, the proliferation, migration and tubule formation ability of HUVECs were inhibited, and autophagy and apoptosis were increased, which were reversed by 3-MA (P < 0.05). After the addition of Sodium-glucose co-transporters 2 inhibitor, Dapagliflozin, the proliferation of HUVECs, the tubule formation, autophagy, apoptosis and migration ability of cells inhibited by HG/PA were significantly improved (P < 0.05). Moreover, the increased protein expression levels of autophagy and apoptosis in HG/PA induced HUVECs were also decreased by the treatment of Dapagliflozin (P < 0.05).
Conclusions: Dapagliflozin can improve the dysfunction of high glucose/high fat-induced human umbilical vein endothelial cells by downregulate autophagy through inhibiting SGLT-2.
Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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