{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T06:14:51Z","timestamp":1774764891669,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Icelandic Technology","award":["187012\u20130611"],"award-info":[{"award-number":["187012\u20130611"]}]},{"name":"Icelandic Technology","award":["FP7 # 601852"],"award-info":[{"award-number":["FP7 # 601852"]}]},{"name":"ASPRE Project EU","award":["187012\u20130611"],"award-info":[{"award-number":["187012\u20130611"]}]},{"name":"ASPRE Project EU","award":["FP7 # 601852"],"award-info":[{"award-number":["FP7 # 601852"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Placental protein 13 (PP13) exhibits a plasma concentration that increases gradually during normal gestation, a process that is disrupted in preeclampsia, which is characterized by elevated vascular resistance, reduced utero-placental blood flow, and intrauterine growth restriction. This study investigated PP13\u2019s role in vascular tone regulation and its molecular mechanisms. Uterine and subcutaneous arteries, isolated from both pregnant and non-pregnant women, were precontracted with the thromboxane analogue U46619 and exposed to PP13 using pressurized myography. The molecular mechanisms were further investigated, using specific inhibitors for nitric oxide synthase (L-NAME+LNNA at 10\u22124 M) and guanylate cyclase (ODQ at 10\u22125 M). The results showed that PP13 induced vasodilation in uterine arteries, but not in subcutaneous arteries. Additionally, PP13 counteracted U46619-induced vasoconstriction, which is particularly pronounced in pregnancy. Further investigation revealed that PP13\u2019s mechanism of action is dependent on the activation of the nitric oxide\u2013cGMP pathway. This study provides novel insights into the vasomodulatory effects of PP13 on human uterine arteries, underscoring its potential role in regulating utero-placental blood flow. These findings suggest that PP13 may be a promising candidate for improving utero-placental blood flow in conditions such as preeclampsia. Further research and clinical studies are warranted to validate PP13\u2019s efficacy and safety as a therapeutic agent for managing preeclampsia.<\/jats:p>","DOI":"10.3390\/ijms25147522","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T08:38:04Z","timestamp":1720514284000},"page":"7522","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Placental Protein 13: Vasomodulatory Effects on Human Uterine Arteries and Potential Implications for Preeclampsia"],"prefix":"10.3390","volume":"25","author":[{"given":"Mariacarmela","family":"Gatto","sequence":"first","affiliation":[{"name":"Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2326-5353","authenticated-orcid":false,"given":"Milena","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0131-6843","authenticated-orcid":false,"given":"Michele","family":"Morelli","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Hospital SS Annunziata, 87100 Cosenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"De Rose","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Hospital SS Annunziata, 87100 Cosenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7824-9752","authenticated-orcid":false,"given":"Sveinbjorn","family":"Gizurarson","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, University of Iceland, 101 Reykjavik, Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamutal","family":"Meiri","sequence":"additional","affiliation":[{"name":"Hylabs Ltd., Rehovot 7670606, Israel"},{"name":"TeleMarpe Ltd., Tel Aviv 6908742, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3736-0205","authenticated-orcid":false,"given":"Maurizio","family":"Mandal\u00e0","sequence":"additional","affiliation":[{"name":"Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Rende, Italy"},{"name":"Department of Obstetrics, Gynecology and Reproductive Sciences, Larner College of Medicine, University of Vermont, Burlington, VT 05401, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.5830\/CVJA-2016-021","article-title":"Physiological changes in pregnancy","volume":"27","author":"Tolppanen","year":"2016","journal-title":"Cardiovasc. 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