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- W4313244849 endingPage "343" @default.
- W4313244849 startingPage "343" @default.
- W4313244849 abstract "Vascular endothelial injury is important in anthracycline-induced cardiotoxicity. Anthracyclines seriously damage the mitochondrial function and mitochondrial homeostasis. In this study, we investigated the damage of epirubicin to vascular endothelial cells and the protective role of metformin from the perspective of mitochondrial homeostasis. We found that epirubicin treatment resulted in DNA double-strand breaks (DSB), elevated reactive oxygen species (ROS) production, and excessive Angiotensin II release in HUVEC cells. Pretreatment with metformin significantly mitigated the injuries caused by epirubicin. In addition, inhibited expression of Mitochondrial transcription factor A (TFAM) and increased mitochondria fragmentation were observed in epirubicin-treated cells, which were partially resumed by metformin pretreatment. In epirubicin-treated cells, knockdown of TFAM counteracted the attenuated DSB formation due to metformin pretreatment, and inhibition of mitochondrial fragmentation with Mdivi-1 decreased DSB formation but increased TFAM expression. Furthermore, epirubicin treatment promoted mitochondrial fragmentation by stimulating the expression of Dynamin-1-like protein (DRP1) and inhibiting the expression of Optic atrophy-1(OPA1) and Mitofusin 1(MFN1), which could be partially prevented by metformin. Finally, we found metformin could increase TFAM expression and decrease DRP1 expression in epirubicin-treated HUVEC cells by upregulating the expression of calcineurin/Transcription factor EB (TFEB). Taken together, this study provided evidence that metformin treatment was an effective way to mitigate epirubicin-induced endothelial impairment by maintaining mitochondrial homeostasis." @default.
- W4313244849 created "2023-01-06" @default.
- W4313244849 creator A5015495757 @default.
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- W4313244849 creator A5043794346 @default.
- W4313244849 creator A5062413350 @default.
- W4313244849 date "2022-12-25" @default.
- W4313244849 modified "2023-09-25" @default.
- W4313244849 title "Metformin Alleviates Epirubicin-Induced Endothelial Impairment by Restoring Mitochondrial Homeostasis" @default.
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- W4313244849 doi "https://doi.org/10.3390/ijms24010343" @default.
- W4313244849 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36613786" @default.
- W4313244849 hasPublicationYear "2022" @default.
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