{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:23:03Z","timestamp":1780446183738,"version":"3.54.1"},"reference-count":81,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T00:00:00Z","timestamp":1681862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R61HL141791"],"award-info":[{"award-number":["R61HL141791"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R33HL141791"],"award-info":[{"award-number":["R33HL141791"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL126974"],"award-info":[{"award-number":["R01HL126974"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32GM122741"],"award-info":[{"award-number":["T32GM122741"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["T32HL069768"],"award-info":[{"award-number":["T32HL069768"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Background<\/jats:title><jats:p>Oral contraceptive (OC) use increases venous thromboembolism risk 2-5-fold. Procoagulant changes can be detected in plasma from OC users even without thrombosis, but cellular mechanisms that provoke thrombosis have not been identified. Endothelial cell (EC) dysfunction is thought to initiate venous thromboembolism. It is unknown whether OC hormones provoke aberrant procoagulant activity in ECs.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Objective<\/jats:title><jats:p>Characterize the effect of high-risk OC hormones (ethinyl estradiol [EE] and drospirenone) on EC procoagulant activity and the potential interplay with nuclear estrogen receptors ER\u03b1 and ER\u03b2 and inflammatory processes.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Methods<\/jats:title><jats:p>Human umbilical vein and dermal microvascular ECs (HUVEC and HDMVEC, respectively) were treated with EE and\/or drospirenone. Genes encoding the estrogen receptors ER\u03b1 and ER\u03b2 (<jats:italic>ESR1<\/jats:italic>and<jats:italic>ESR2<\/jats:italic>, respectively) were overexpressed in HUVEC and HDMVEC via lentiviral vectors. EC gene expression was assessed by RT-qPCR. The ability of ECs to support thrombin generation and fibrin formation was measured by calibrated automated thrombography and spectrophotometry, respectively.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Results<\/jats:title><jats:p>Neither EE nor drospirenone, alone or together, changed expression of genes encoding anti- or procoagulant proteins (<jats:italic>TFPI<\/jats:italic>,<jats:italic>THBD<\/jats:italic>,<jats:italic>F3<\/jats:italic>), integrins (<jats:italic>ITGAV<\/jats:italic>,<jats:italic>ITGB3<\/jats:italic>), or fibrinolytic mediators (<jats:italic>SERPINE1<\/jats:italic>,<jats:italic>PLAT<\/jats:italic>). EE and\/or drospirenone did not increase EC-supported thrombin generation or fibrin formation, either. Our analyses indicated a subset of individuals express<jats:italic>ESR1<\/jats:italic>and<jats:italic>ESR2<\/jats:italic>transcripts in human aortic ECs. However, overexpression of<jats:italic>ESR1<\/jats:italic>and\/or<jats:italic>ESR2<\/jats:italic>in HUVEC and HDMVEC did not facilitate the ability of OC-treated ECs to support procoagulant activity, even in the presence of a pro-inflammatory stimulus.<\/jats:p><\/jats:sec><jats:sec id=\"sec005\"><jats:title>Conclusions<\/jats:title><jats:p>The OC hormones EE and drospirenone do not directly enhance thrombin generation potential of primary ECs<jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0284333","type":"journal-article","created":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T17:29:48Z","timestamp":1681925388000},"page":"e0284333","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["High risk oral contraceptive hormones do not directly enhance endothelial cell procoagulant activity in vitro"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1481-3059","authenticated-orcid":true,"given":"Emma G.","family":"Bouck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marios","family":"Arvanitis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William O.","family":"Osburn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqiu","family":"Sang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Reventun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Homa K.","family":"Ahmadzia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas L.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles J.","family":"Lowenstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2845-2303","authenticated-orcid":true,"given":"Alisa S.","family":"Wolberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,4,19]]},"reference":[{"key":"pone.0284333.ref001","first-page":"150","article-title":"Universal access to contraception: women, families, and communities benefit.","volume":"222","author":"LW Rice","year":"2020","journal-title":"Am J Obstet Gynecol"},{"key":"pone.0284333.ref002","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0140-6736(12)60478-4","article-title":"Maternal deaths averted by contraceptive use: An analysis of 172 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