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Liraglutide Improves Endothelial Function via the mTOR Signaling Pathway
Han Wu1, Cheng Xiao1, Yiting Zhao2
1Department of Endocrinology, Key Laboratory of Endocrinology, National Health Commission, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
Liraglutide protects endothelial cells by activating the mTORC2/Akt pathway, enhancing nitric oxide production and reducing apoptosis. This study reveals a novel mechanism for liraglutide
Area of Science:
- Endothelial biology and cellular signaling.
- Molecular mechanisms of drug action.
- Cardiovascular disease research.
Background:
- Mammalian target of rapamycin (mTOR) signaling is vital for maintaining endothelial cell function.
- Endothelial dysfunction is a key factor in various cardiovascular diseases.
- The role of GLP-1 analogues, like liraglutide, in endothelial health requires further elucidation.
Purpose of the Study:
- To investigate the protective effects of liraglutide on endothelial cells.
- To determine if liraglutide modulates endothelial function through the mTOR signaling pathway.
Main Methods:
- Human umbilical vein endothelial cells (HUVECs) were treated with liraglutide.
- Western blot and immunoprecipitation assessed mTOR, mTORC1, and mTORC2 expression and phosphorylation.
- Nitric oxide (NO) release, eNOS phosphorylation, hTERT activity, and apoptosis markers were quantified.
Main Results:
- Liraglutide induced sustained mTOR phosphorylation and mTORC2 formation, leading to Akt phosphorylation.
- Enhanced NO production and eNOS phosphorylation were observed, mediated by mTORC2/Akt activation.
- Liraglutide demonstrated antiapoptotic effects by modulating key protein expressions.
Conclusions:
- Liraglutide significantly improves endothelial function.
- The protective effects are, at least partially, mediated by the mTORC2/Akt signaling pathway.
- Liraglutide represents a potential therapeutic agent for endothelial dysfunction.
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