{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T02:40:35Z","timestamp":1785465635241,"version":"3.56.0"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1142636"],"award-info":[{"award-number":["1142636"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Norman Beischer Medical Research Foundation Fellowship grant"},{"name":"National Health and Medical Research Foundation","award":["1146128"],"award-info":[{"award-number":["1146128"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Preeclampsia is a multi-system disease that can have severe, even fatal implications for the mother and fetus. Abnormal placentation can lead to ischaemic tissue injury and placental inflammation. In turn, the placenta releases anti-angiogenic factors into the maternal circulation. These systemically act to neutralise angiogenic factors causing endothelial dysfunction causing preeclampsia. Hydroxychloroquine is an immune modulating drug that is considered safe in pregnancy. There is epidemiological evidence suggesting it may reduce the risk of preeclampsia. Here, we examined the effects hydroxychloroquine on the production and secretion of sFlt-1, soluble endoglin (sENG), placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) in primary human placenta, cytotrophoblasts and umbilical vein endothelial cells (endothelial cell model). Hydroxychloroquine treatment decreased mRNA expression of two sFlt-1 isoforms and its protein secretion. sENG was not reduced. Hydroxychloroquine treatment increased secretion of pro-angiogenic factor PIGF from endothelial cells. It did not significantly reduce the expression of the endothelial cell inflammation marker, <jats:italic>ET-1<\/jats:italic>, and inflammation induced expression of the adhesion molecule, <jats:italic>VCAM<\/jats:italic>. Hydroxychloroquine could not overcome leukocyte adhesion to endothelial cells. Hydroxychloroquine mitigates features of preeclampsia, but it does not reduce key markers of endothelial dysfunction.<\/jats:p>","DOI":"10.1371\/journal.pone.0271560","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T14:57:26Z","timestamp":1669301846000},"page":"e0271560","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Hydroxychloroquine reduces soluble Flt-1 secretion from human cytotrophoblast, but does not mitigate markers of endothelial dysfunction in vitro"],"prefix":"10.1371","volume":"17","author":[{"given":"Elif","family":"Kadife","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Hannan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alesia","family":"Harper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Binder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Beard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1439-7016","authenticated-orcid":true,"given":"Fiona C.","family":"Brownfoot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,11,23]]},"reference":[{"issue":"1","key":"pone.0271560.ref001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejogrb.2013.05.005","article-title":"Global and regional estimates of preeclampsia and eclampsia: a systematic review","volume":"170","author":"E Abalos","year":"2013","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"issue":"7","key":"pone.0271560.ref002","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1161\/CIRCRESAHA.118.313276","article-title":"Preeclampsia: Pathophysiology, Challenges, and Perspectives","volume":"124","author":"S Rana","year":"2019","journal-title":"Circ Res"},{"key":"pone.0271560.ref003","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.preghy.2018.05.004","article-title":"The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice","volume":"13","author":"MA Brown","year":"2018","journal-title":"Pregnancy Hypertension"},{"issue":"7","key":"pone.0271560.ref004","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.3390\/jcm9072245","article-title":"Preeclampsia Is a Syndrome with a Cascade of Pathophysiologic Events","volume":"9","author":"W. 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