GLP-1 and Ghrelin Attenuate High Glucose/High Lipid-Induced Apoptosis and Senescence of Human Microvascular Endothelial CellsLiao P. · Yang D. · Liu D. · Zheng Y.
Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Department of Vascular Surgery,
Peking Union Medical College Hospital,
Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, (China)
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Background/Aims: GLP-1 and ghrelin are common appetite-regulating hormones. Both have multiple functions beyond metabolic regulation. However, the effects of GLP-1 and ghrelin on endothelial biology are not fully understood. Here, we investigate the roles of GLP-1 and ghrelin in microvascular endothelial apoptosis and senescence. Methods: Human microvascular endothelial cells (HMECs) were exposed to high glucose/high lipid (HG/HL) conditions and treated with GLP-1 or ghrelin. Cellular apoptosis, senescence, and mitochondrial function were measured. In addition, the MAPK and Akt signaling pathways were examined. Results: Both GLP-1 and ghrelin treatment decreased the number of TUNEL-positive cells and inhibited caspase-3 and PARP cleavage and mitochondrial dysfunction in HG/HL-exposed HMECs. GLP-1, but not ghrelin decreased the number of β-galactosidase (β-gal)-positive cells. Furthermore, GLP-1 and ghrelin inhibited ERK1/2, JNK1/2, and p38 signaling. GLP-1 suppressed Akt signaling, but ghrelin had no effect. Moreover, JNK1/2 and p38 inhibitors, but not ERK1/2 and Akt inhibitors, decreased the number of TUNEL-positive cells. Additionally, only the Akt inhibitor decreased the number of β-gal-positive cells. Conclusion: These results demonstrate that GLP-1 and ghrelin inhibit mitochondrial dysfunction under HG/HL conditions, and suppress endothelial apoptosis via inhibiting JNK1/2 and p38 signaling; moreover, GLP-1 alleviates endothelial senescence via inactivating Akt signaling.
© 2017 The Author(s). Published by S. Karger AG, Basel
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Article / Publication Details
Received: June 23, 2017
Accepted: October 14, 2017
Published online: December 07, 2017
Issue release date: Published online first (Issue-in-Progress)
Number of Print Pages: 14
Number of Figures: 7
Number of Tables: 0
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