{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T21:17:11Z","timestamp":1791753431868,"version":"4.3.4"},"reference-count":51,"publisher":"Portland Press Ltd.","issue":"6","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,12,1]]},"abstract":"<jats:p>Pre-eclampsia, a pregnancy-specific multi-organ syndrome characterized by widespread endothelial damage, is a new risk factor for cardiovascular disease. No therapies exist to prevent or treat this condition, even to achieve a modest improvement in pregnancy length or birth weight. Co-administration of soluble VEGFR-1 [VEGF (vascular endothelial growth factor) receptor-1; more commonly known as sFlt-1 (soluble Fms-like tyrosine kinase-1)] and sEng (soluble endoglin) to pregnant rats elicits severe pre-eclampsia-like symptoms. These two anti-angiogenic factors are increased dramatically prior to the clinical onset of pre-eclampsia and are quite possibly the \u2018final common pathway\u2019 responsible for the accompanying signs of hypertension and proteinuria as they can be reversed by VEGF administration in animal models. HO-1 (haem oxygenase-1), an anti-inflammatory enzyme, and its metabolite, CO (carbon monoxide), exert protective effects in several organs against oxidative stimuli. In a landmark publication, we showed that the HO-1 pathway inhibits sFlt-1 and sEng in cultured cells and human placental tissue explants. Both CO and NO (nitric oxide) promote vascular homoeostasis and vasodilatation, and activation of VEGFR-1 or VEGFR-2 induced eNOS (endothelial nitric oxide synthase) phosphorylation, NO release and HO-1 expression. Our studies established the HO-1\/CO pathway as a negative regulator of cytokine-induced sFlt-1 and sEng release and eNOS as a positive regulator of VEGF-mediated vascular morphogenesis. These findings provide compelling evidence for a protective role of HO-1 in pregnancy and identify it as a target for the treatment of pre-eclampsia. Any agent that is known to up-regulate HO-1, such as statins, may have potential as a therapy. Any intervention achieving even a modest prolongation of pregnancy or amelioration of the condition could have a significant beneficial health impact worldwide.<\/jats:p>","DOI":"10.1042\/bst0371237","type":"journal-article","created":{"date-parts":[[2009,11,19]],"date-time":"2009-11-19T18:02:29Z","timestamp":1258653749000},"page":"1237-1242","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Can the biology of VEGF and haem oxygenases help solve pre-eclampsia?"],"prefix":"10.1042","volume":"37","author":[{"given":"Asif","family":"Ahmed","sequence":"first","affiliation":[{"name":"Department of Reproductive and Vascular Biology, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, U.K."},{"name":"Birmingham Women's Hospital, Edgbaston, Birmingham B15 2TG, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa\u00a0J.","family":"Cudmore","sequence":"additional","affiliation":[{"name":"Department of Reproductive and Vascular Biology, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, U.K."},{"name":"Birmingham Women's Hospital, Edgbaston, Birmingham B15 2TG, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2009,11,19]]},"reference":[{"key":"2021111719311491900_B1","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1126\/science.1111726","article-title":"Latest advances in understanding preeclampsia","volume":"308","author":"Redman","year":"2005","journal-title":"Science"},{"key":"2021111719311491900_B2","doi-asserted-by":"crossref","first-page":"326.e1","DOI":"10.1016\/j.ajog.2006.11.002","article-title":"Identification of patients at risk for early onset and\/or severe preeclampsia with the use of uterine artery Doppler velocimetry and placental growth factor","volume":"196","author":"Espinoza","year":"2007","journal-title":"Am. 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