{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T03:31:14Z","timestamp":1772767874017,"version":"3.50.1"},"reference-count":55,"publisher":"Wiley","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008958","name":"Lawson Health Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008958","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Disease Markers"],"published-print":{"date-parts":[[2016]]},"abstract":"<jats:p>In intrauterine growth restriction (IUGR), a subset of pregnancies undergoes placental vascular dysregulation resulting in restricted blood flow and fetal hypoxemia. Altered transcription of hypoxic regulated plasminogen activator inhibitor 1 (PAI-1) has been associated with pregnancy complications and angiogenic regulation. Here we assessed circulating PAI-1 as an indicator of placental insufficiency. Venous umbilical PAI-1 of hypoxemic (V<jats:italic>p<\/jats:italic>O<jats:sub>2<\/jats:sub>20 versus 35\u2009mmHg,<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mi>p<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn fontstyle=\"italic\">0.0001<\/mml:mn><\/mml:math>) placental insufficient pregnancies (resistance index 0.9 versus 0.63,<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mi>p<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn fontstyle=\"italic\">0.05<\/mml:mn><\/mml:math>) (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\"><mml:mi>n<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn fontstyle=\"italic\">18<\/mml:mn><\/mml:math>) was compared to controls (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\"><mml:mi>n<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn fontstyle=\"italic\">12<\/mml:mn><\/mml:math>). PAI-1 was increased (~10-fold,<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\"><mml:mi>p<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn fontstyle=\"italic\">0.001<\/mml:mn><\/mml:math>) and had a positive predictive ratio of 6.7. Further, PAI-1 levels correlated to blood oxygen (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M6\"><mml:mi>r<\/mml:mi><mml:mo>=<\/mml:mo><mml:mo>-<\/mml:mo><mml:mn fontstyle=\"italic\">0.68<\/mml:mn><\/mml:math>,<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M7\"><mml:mi>p<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn fontstyle=\"italic\">0.0001<\/mml:mn><\/mml:math>). The plasma\u2019s angiogenic potency measured<jats:italic>in vitro<\/jats:italic>was associated with umbilical cord blood PAI-1 levels (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M8\"><mml:mi>r<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn fontstyle=\"italic\">0.65<\/mml:mn><\/mml:math>,<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M9\"><mml:mi>p<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn fontstyle=\"italic\">0.01<\/mml:mn><\/mml:math>). This association was attenuated by PAI-1 inhibiting antibody (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M10\"><mml:mi>p<\/mml:mi><mml:mo>&lt;<\/mml:mo><mml:mn fontstyle=\"italic\">0.001<\/mml:mn><\/mml:math>). The results demonstrate PAI-1 as a potential marker of placental insufficiency and identify its close association with pathological hypoxia and angiogenesis in a subset of growth restricted pregnancies.<\/jats:p>","DOI":"10.1155\/2016\/7124186","type":"journal-article","created":{"date-parts":[[2016,1,19]],"date-time":"2016-01-19T21:34:04Z","timestamp":1453239244000},"page":"1-13","source":"Crossref","is-referenced-by-count":26,"title":["Increased Umbilical Cord PAI-1 Levels in Placental Insufficiency Are Associated with Fetal Hypoxia and Angiogenesis"],"prefix":"10.1155","volume":"2016","author":[{"given":"Maxim D.","family":"Seferovic","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhulika B.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Children\u2019s Health Research Institute, Departments of Biochemistry and Pediatrics, University of Western Ontario, London, ON, Canada N6C 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