{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:22:06Z","timestamp":1788916926597,"version":"build-2803163510"},"reference-count":70,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:00:00Z","timestamp":1708473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/17\/8\/32924"],"award-info":[{"award-number":["RG\/17\/8\/32924"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/14\/5\/30547"],"award-info":[{"award-number":["PG\/14\/5\/30547"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Gestational hypoxia adversely affects uterine artery function, increasing complications. However, an effective therapy remains unidentified. Here, we show in rodent uterine arteries that hypoxic pregnancy promotes hypertrophic remodelling, increases constrictor reactivity via protein kinase C signalling, and triggers compensatory dilatation via nitric oxide\u2010dependent mechanisms and stimulation of large conductance Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup>\u2010channels. Maternal <jats:italic>in vivo<\/jats:italic> oral treatment with the mitochondria\u2010targeted antioxidant MitoQ in hypoxic pregnancy normalises uterine artery reactivity and prevents vascular remodelling. From days 6\u201320 of gestation (term \u223c22 days), female Wistar rats were randomly assigned to normoxic or hypoxic (13\u201314% O<jats:sub>2<\/jats:sub>) pregnancy\u00a0\u00b1\u00a0daily maternal MitoQ treatment (500 \u00b5<jats:sc>m<\/jats:sc> in drinking water). At 20 days of gestation, maternal, placental and fetal tissue was frozen to determine MitoQ uptake. The uterine arteries were harvested and, in one segment, constrictor and dilator reactivity was determined by wire myography. Another segment was fixed for unbiased stereological analysis of vessel morphology. Maternal administration of MitoQ in both normoxic and hypoxic pregnancy crossed the placenta and was present in all tissues analysed. Hypoxia increased uterine artery constrictor responses to norepinephrine, angiotensin II and the protein kinase C activator, phorbol 12,13\u2010dibutyrate. Hypoxia enhanced dilator reactivity to sodium nitroprusside, the large conductance Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup>\u2010channel activator NS1619 and ACh via increased nitric oxide\u2010dependent mechanisms. Uterine arteries from hypoxic pregnancy showed increased wall thickness and MitoQ treatment in hypoxic pregnancy prevented all effects on uterine artery reactivity and remodelling. The data support mitochondria\u2010targeted therapy against adverse changes in uterine artery structure and function in high\u2010risk pregnancy.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15950-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Dysfunction and remodelling of the uterine artery are strongly implicated in many pregnancy complications, including advanced maternal age, maternal hypertension of pregnancy, maternal obesity, gestational diabetes and pregnancy at high altitude.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Such complications not only have immediate adverse effects on the growth of the fetus, but also they can also increase the risk of cardiovascular disease in the mother and offspring. Despite this, there is a significant unmet clinical need for therapeutics that treat uterine artery vascular dysfunction in adverse pregnancy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Here, we show in a rodent model of gestational hypoxia that <jats:italic>in vivo<\/jats:italic> oral treatment of the mitochondria\u2010targeted antioxidant MitoQ protects against uterine artery vascular dysfunction and remodelling, supporting the use of mitochondria\u2010targeted therapy against adverse changes in uterine artery structure and function in high\u2010risk pregnancy.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp286178","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T14:49:35Z","timestamp":1708526975000},"page":"1211-1225","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["<i>In vivo<\/i> mitochondria\u2010targeted protection against uterine artery vascular dysfunction and remodelling in rodent hypoxic pregnancy"],"prefix":"10.1113","volume":"602","author":[{"given":"Zhongchao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Physiology, Development and Neuroscience University of Cambridge  Cambridge UK"},{"name":"Department of Aerospace Physiology Fourth Military Medical University  Xi'an China"},{"name":"Department of Congenital Heart Disease General Hospital of Northern Theater Command  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0767-2697","authenticated-orcid":false,"given":"Emily J.","family":"Camm","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development and Neuroscience University of Cambridge  Cambridge UK"},{"name":"The Ritchie Centre Hudson Institute of Medical Research  Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna 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Development and Neuroscience University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6730-8067","authenticated-orcid":false,"given":"Alessandro","family":"Rolfo","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3016-1510","authenticated-orcid":false,"given":"Tullia","family":"Todros","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Logan","sequence":"additional","affiliation":[{"name":"MRC Mitochondrial Biology Unit University of Cambridge  Cambridge 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