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We also aimed to determine the relationships between circulating TIMP\u20103 and matrix metalloproteinase 2 (MMP\u20102), MMP\u20109, TIMP\u20101, and TIMP\u20102 concentrations in pre\u2010eclampsia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A primary case\u2013control study included patients with pre\u2010eclampsia (<jats:italic>n<\/jats:italic>\u00a0=\u2009219) and gestational hypertension (<jats:italic>n<\/jats:italic>\u00a0=\u2009118), healthy pregnant women (<jats:italic>n<\/jats:italic>\u00a0=\u2009214), and non\u2010pregnant women (<jats:italic>n<\/jats:italic>\u00a0=\u200966), and a replication case\u2013control study included patients with pre\u2010eclampsia (<jats:italic>n<\/jats:italic>\u00a0=\u2009177) and healthy pregnant women (<jats:italic>n<\/jats:italic>\u00a0=\u2009124), all from southeastern Brazil. Plasma TIMP\u20103, MMP\u20102, MMP\u20109, TIMP\u20101, and TIMP\u20102 concentrations were assessed using commercially available enzyme\u2010linked immunosorbent assay kits, and the relationships between them were analyzed using Spearman's correlation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In our primary study, patients with pre\u2010eclampsia and gestational hypertension exhibited increased TIMP\u20103 concentrations compared with healthy pregnant women (both <jats:italic>P<\/jats:italic>\u00a0&lt;\u20090.0001) and non\u2010pregnant women (both <jats:italic>P<\/jats:italic>\u00a0&lt;\u20090.001). These findings were confirmed in the replication study, showing elevated TIMP\u20103 concentrations in women with pre\u2010eclampsia versus healthy pregnant women (<jats:italic>P<\/jats:italic>\u00a0&lt;\u20090.001). We found no difference in TIMP\u20103 concentrations between early\u2010onset and late\u2010onset pre\u2010eclampsia. Moreover, TIMP\u20103 concentrations were significantly correlated with plasma concentrations of TIMP\u20101 (<jats:italic>r<\/jats:italic>\u00a0=\u20090.2333; <jats:italic>P<\/jats:italic>\u00a0=\u20090.0086) and MMP\u20102 (<jats:italic>r<\/jats:italic>\u00a0=\u20090.2159; <jats:italic>P<\/jats:italic>\u00a0=\u20090.0156) in pre\u2010eclampsia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Circulating TIMP\u20103 concentration is increased in women with pre\u2010eclampsia compared with healthy pregnant women, and it is positively correlated with plasma MMP\u20102 and TIMP\u20101 concentrations in pre\u2010eclampsia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ijgo.14552","type":"journal-article","created":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T08:15:31Z","timestamp":1667636131000},"page":"544-551","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Circulating levels of tissue inhibitor of metalloproteinase 3, a protein with inhibitory effects on angiogenesis, are increased in pre\u2010eclampsia"],"prefix":"10.1002","volume":"161","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2669-5301","authenticated-orcid":false,"given":"Ana C.","family":"Palei","sequence":"first","affiliation":[{"name":"Department of Surgery, School of Medicine University of Mississippi Medical Center  Jackson Mississippi USA"},{"name":"Cardiovascular\u2010Renal Research Center University of Mississippi Medical Center  Jackson Mississippi USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana de O.","family":"Cruz","sequence":"additional","affiliation":[{"name":"Department of Genetics, Ecology and Evolution Institute of Biological Sciences Federal University of Minas Gerais  Belo Horizonte Minas Gerais Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Leandro","family":"Chaguri","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Pharmacology Institute of Biosciences of Botucatu Sao Paulo State University (Unesp)  Botucatu Sao Paulo Brazil"},{"name":"Center of Toxicological Assistance (CEATOX) Institute of Biosciences of Botucatu Sao Paulo State University (Unesp)  Botucatu Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3273-3001","authenticated-orcid":false,"given":"Jos\u00e9\u00a0Carlos","family":"Pera\u00e7oli","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics Botucatu Medical School Sao Paulo State University (Unesp)  Botucatu Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8990-0237","authenticated-orcid":false,"given":"Mariana","family":"Rom\u00e3o\u2010Veiga","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics Botucatu Medical School Sao Paulo State University (Unesp)  Botucatu Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa R.","family":"Ribeiro\u2010Vasques","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biological Sciences Institute of Biosciences of Botucatu Sao Paulo State University (Unesp)  Botucatu Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5010-4914","authenticated-orcid":false,"given":"Ricardo C.","family":"Cavalli","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Faculty of Medicine of Ribeirao Preto University of Sao Paulo (USP)  Botucatu Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8041-5753","authenticated-orcid":false,"given":"Priscila R.","family":"Nunes","sequence":"additional","affiliation":[{"name":"Department of 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