{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T11:16:14Z","timestamp":1784632574522,"version":"3.55.0"},"reference-count":77,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,25]],"date-time":"2022-12-25T00:00:00Z","timestamp":1671926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002367","name":"Hefei Science Center CAS","doi-asserted-by":"publisher","award":["2020HSC-UE018"],"award-info":[{"award-number":["2020HSC-UE018"]}],"id":[{"id":"10.13039\/501100002367","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002367","name":"Hefei Science Center CAS","doi-asserted-by":"publisher","award":["11575232"],"award-info":[{"award-number":["11575232"]}],"id":[{"id":"10.13039\/501100002367","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2020HSC-UE018"],"award-info":[{"award-number":["2020HSC-UE018"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["11575232"],"award-info":[{"award-number":["11575232"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms24010343","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T04:40:39Z","timestamp":1672116039000},"page":"343","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Metformin Alleviates Epirubicin-Induced Endothelial Impairment by Restoring Mitochondrial Homeostasis"],"prefix":"10.3390","volume":"24","author":[{"given":"Qi","family":"Sun","sequence":"first","affiliation":[{"name":"The Center for Ion Beam Bioengineering & Green Agriculture, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China"},{"name":"The Science Island Branch of the Graduate School, University of Science and Technology of China, Hefei 230031, China"},{"name":"USTC Life Sciences and Medicine, University of Science and Technology of China, Hefei 230031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5559-5422","authenticated-orcid":false,"given":"Huiling","family":"Jia","sequence":"additional","affiliation":[{"name":"The Center for Ion Beam Bioengineering & Green Agriculture, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Cheng","sequence":"additional","affiliation":[{"name":"The Center for Ion Beam Bioengineering & Green Agriculture, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2648-0850","authenticated-orcid":false,"given":"Yujuan","family":"Wang","sequence":"additional","affiliation":[{"name":"High Magnetic Field Laboratory of the Chinese Academy of Sciences, Hefei 230031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"The Center for Ion Beam Bioengineering & Green Agriculture, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1002\/cncr.11407","article-title":"Congestive heart failure in patients treated with doxorubicin\u2014A retrospective analysis of three trials","volume":"97","author":"Swain","year":"2003","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1016\/j.jacc.2013.02.072","article-title":"Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: The OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies)","volume":"61","author":"Bosch","year":"2013","journal-title":"J. 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