{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T23:37:44Z","timestamp":1783381064945,"version":"3.54.6"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100014688","name":"Region Uppsala","doi-asserted-by":"publisher","award":["LUL-915281"],"award-info":[{"award-number":["LUL-915281"]}],"id":[{"id":"10.13039\/501100014688","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Swedish Society for Medical Research, Sweden"},{"DOI":"10.13039\/501100001862","name":"The Swedish Research Council","doi-asserted-by":"crossref","award":["2020- 01026"],"award-info":[{"award-number":["2020- 01026"]}],"id":[{"id":"10.13039\/501100001862","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007051","name":"Uppsala University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007051","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Preeclampsia and cardiovascular disease (CVD) share multiple features and risk factors. Circulating angiotensin-converting enzyme 2 (ACE2) is increased in CVD and mediates SARS-CoV-2 entry into host cells, causing COVID-19 infection. The role of ACE2 in preeclampsia pathophysiology is unknown. We hypothesized that circulating ACE2 is increased in mid-pregnancy in women later developing preeclampsia. We included 296 women later developing preeclampsia (cases) and 333 women with a continuous healthy pregnancy (controls). Circulating ACE2 was measured with an immunoassay based on proximity extension assay technology, with levels being expressed as relative quantification on a log2 scale. Median (interquartile range) ACE2 levels were higher in cases than in controls; 3.84 (3.50\u20134.24) vs. 3.72 (3.45\u20134.04), <jats:italic>p<\/jats:italic>\u2009=\u20090.002. Adjusted logistic regression models showed a 60% increased risk for later development of preeclampsia with one unit elevation of ACE2 (adjusted odds ratio (aOR) 1.60, 95% confidence intervals (CI) 1.17\u20132.18). Preterm preeclampsia (diagnosis before 37 gestational weeks, <jats:italic>n<\/jats:italic>\u2009=\u200997) seemed to have a stronger ACE2 association than term preeclampsia, <jats:italic>n<\/jats:italic>\u2009=\u2009199 (aORs, 95% Cis 2.14, 1.15\u20133.96 and 1.52, 1.04\u20132.23, respectively). Circulating ACE2 is increased at mid-pregnancy in women later developing preeclampsia, particularly preterm preeclampsia. Thus, our finding indicates a partly shared pathophysiological pathway between preeclampsia and CVD.<\/jats:p>","DOI":"10.1038\/s41598-022-08081-8","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T17:03:30Z","timestamp":1646759010000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Elevated mid-pregnancy plasma levels of angiotensin-converting enzyme 2 in women prior to the development of preeclampsia"],"prefix":"10.1038","volume":"12","author":[{"given":"Katja","family":"Junus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inger","family":"Bj\u00f6rk Ragnarsd\u00f3ttir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paliz","family":"Nordl\u00f6f Callbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Bergman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Lager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Karin","family":"Wikstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"8081_CR1","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1053\/j.semperi.2011.09.011","volume":"36","author":"L Ghulmiyyah","year":"2012","unstructured":"Ghulmiyyah, L. & Sibai, B. Maternal mortality from preeclampsia\/eclampsia. Semin. Perinatol. 36, 56\u201359 (2012).","journal-title":"Semin. Perinatol."},{"key":"8081_CR2","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1161\/CIRCULATIONAHA.118.038080","volume":"140","author":"LJ Leon","year":"2019","unstructured":"Leon, L. J. et al. Preeclampsia and cardiovascular disease in a large UK pregnancy cohort of linked electronic health records: A CALIBER study. Circulation 140, 1050\u20131060 (2019).","journal-title":"Circulation"},{"key":"8081_CR3","doi-asserted-by":"publisher","first-page":"e12917","DOI":"10.1097\/MD.0000000000012917","volume":"97","author":"Q Zhang","year":"2018","unstructured":"Zhang, Q. et al. Association of angiotensin-converting enzyme 2 gene polymorphism and enzymatic activity with essential hypertension in different gender: A case\u2013control study. 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