{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:49:10Z","timestamp":1787503750410,"version":"build-2736575974"},"reference-count":35,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2017,7,30]],"date-time":"2017-07-30T00:00:00Z","timestamp":1501372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JFB"],"abstract":"<jats:p>The molecular mechanisms of pre-eclampsia are being increasingly clarified in animals and humans. With the uncovering of these mechanisms, preventive therapy strategies using chronic infusion of adrenomedullin, vascular endothelial growth factor-121 (VEGF-121), losartan, and sildenafil have been proposed to block narrow spiral artery formation in the placenta by suppressing related possible factors for pre-eclampsia. However, although such preventive treatments have been partly successful, they have failed in ameliorating fetal growth restriction and carry the risk of possible side-effects of drugs on pregnant mothers. In this study, we attempted to develop a new symptomatic treatment for pre-eclampsia by directly rescuing placental ischemia with artificial oxygen carriers (hemoglobin vesicles: HbV) since previous data indicate that placental ischemia\/hypoxia may alone be sufficient to lead to pre-eclampsia through up-regulation of sFlt-1, one of the main candidate molecules for the cause of pre-eclampsia. Using a rat model, the present study demonstrated that a simple treatment using hemoglobin vesicles for placental ischemia rescues placental and fetal hypoxia, leading to appropriate fetal growth. The present study is the first to demonstrate hemoglobin vesicles successfully decreasing maternal plasma levels of sFlt-1 and ameliorating fetal growth restriction in the pre-eclampsia rat model (p &lt; 0.05, one-way ANOVA). In future, chronic infusion of hemoglobin vesicles could be a potential effective and noninvasive therapy for delaying or even alleviating the need for Caesarean sections in pre-eclampsia.<\/jats:p>","DOI":"10.3390\/jfb8030032","type":"journal-article","created":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T03:30:06Z","timestamp":1501558206000},"page":"32","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Potential New Non-Invasive Therapy Using Artificial Oxygen Carriers for Pre-Eclampsia"],"prefix":"10.3390","volume":"8","author":[{"given":"Hidenobu","family":"Ohta","sequence":"first","affiliation":[{"name":"Department of Psychophysiology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8553, Japan"},{"name":"Department of Psychiatry, Asai Hospital, Togane, Chiba 283-0042, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiko","family":"Kaga","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Hospital Organization Sendai Medical Center, Miyagino-Ku, Sendai, Miyagi 983-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0681-3032","authenticated-orcid":false,"given":"Hiromi","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Medicine, School of Medicine, Nara Medical University, Kashihara, Nara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunihiro","family":"Okamura","sequence":"additional","affiliation":[{"name":"Tohoku Kosai Hospital, Aoba-ku, Sendai, Miyagi 980-0803, Japan"},{"name":"Department of Obstetrics and Gynecology, Tohoku University Hospital, Aoba-ku, Sendai, Miyagi 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2521-039X","authenticated-orcid":false,"given":"Nobuo","family":"Yaegashi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Tohoku University Hospital, Aoba-ku, Sendai, Miyagi 980-8574, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/S0140-6736(05)17987-2","article-title":"Pre-eclampsia","volume":"365","author":"Sibai","year":"2005","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1001\/jama.2017.3439","article-title":"Screening for preeclampsia: US Preventive Services Task Force recommendation statement","volume":"317","author":"Grossman","year":"2017","journal-title":"JAMA."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1001\/jama.2016.18315","article-title":"Preeclampsia screening: Evidence report and systematic review for the US Preventive Services Task Force","volume":"317","author":"Henderson","year":"2017","journal-title":"JAMA."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/j.1538-7836.2008.03259.x","article-title":"Vascular biology of preeclampsia","volume":"7","author":"Myatt","year":"2009","journal-title":"J. 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