{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T09:54:33Z","timestamp":1769334873259,"version":"3.49.0"},"reference-count":69,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["2020.06616.BD"],"award-info":[{"award-number":["2020.06616.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["Project Centro-01-0145-FEDER-000019\u2014C4\u2014Centro de Compet\u00eancias em Cloud Computing"],"award-info":[{"award-number":["Project Centro-01-0145-FEDER-000019\u2014C4\u2014Centro de Compet\u00eancias em Cloud Computing"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["UIDB\/00709\/2020"],"award-info":[{"award-number":["UIDB\/00709\/2020"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioMedInformatics"],"abstract":"<jats:p>Metformin is the most used oral anti-diabetic drug in the world and consequently is commonly found in the aquatic environment. Some studies demonstrated that metformin may act as an endocrine-disrupting-chemical (EDC) in fish, although it does not have a classic EDC structure. In this sense, the aim of this work was to evaluate the potential disrupting effect of metformin in the cardiovascular system through in vitro, ex vivo, and in silico studies. For this purpose, human umbilical artery (HUA) and rat aorta artery (RAA) were used. The toxic concentrations of metformin were determined by a cytotoxicity assay and in silico simulations were performed to analyze the interactions of metformin with hormonal receptors. Our results show that metformin decreases viability of the smooth muscle cells. Moreover, metformin induces a vasorelaxant effect in rat aorta and human models by an endothelium-dependent and -independent pathways. Furthermore, docking simulations showed that metformin binds to androgen receptors (AR) and estrogen receptors (ER\u03b1 and ER\u03b2). In conclusion, the in silico assays suggested that metformin has the potential to be an endocrine disruptor, acting mainly on ER\u03b1. Further studies are needed to use metformin in pregnant women without impairing the cardiovascular health of the future generation.<\/jats:p>","DOI":"10.3390\/biomedinformatics2020014","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T12:20:25Z","timestamp":1648038025000},"page":"217-233","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Protein Interaction Network for Identifying Vascular Response of Metformin (Oral Antidiabetic)"],"prefix":"10.3390","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9934-7394","authenticated-orcid":false,"given":"Margarida","family":"Baptista","sequence":"first","affiliation":[{"name":"Health Sciences Research Centre, CICS-UBI, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"},{"name":"Faculty of Health Sciences, FCS-UBI, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4752-6398","authenticated-orcid":false,"given":"Margarida","family":"Lorigo","sequence":"additional","affiliation":[{"name":"Health Sciences Research Centre, CICS-UBI, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"},{"name":"Faculty of Health Sciences, FCS-UBI, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"Cloud Computing Competence Centre, C4-UBI, University of Beira Interior, 6200-501 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4823-5701","authenticated-orcid":false,"given":"Elisa","family":"Cairrao","sequence":"additional","affiliation":[{"name":"Health Sciences Research Centre, CICS-UBI, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"},{"name":"Faculty of Health Sciences, FCS-UBI, University of Beira Interior, 6201-506 Covilh\u00e3, Portugal"},{"name":"Cloud Computing Competence Centre, C4-UBI, University of Beira Interior, 6200-501 Covilh\u00e3, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.cmet.2014.09.018","article-title":"Metformin: From mechanisms of action to therapies","volume":"20","author":"Foretz","year":"2014","journal-title":"Cell Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"81","DOI":"10.2165\/11534750-000000000-00000","article-title":"Clinical pharmacokinetics of metformin","volume":"50","author":"Graham","year":"2011","journal-title":"Clin. 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