title: Increased Umbilical Cord PAI-1 Levels in Placental Insufficiency Are Associated with Fetal Hypoxia and Angiogenesis.
abstract: 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 (VpO2 20 versus 35 mmHg, p < 0.0001) placental insufficient pregnancies (resistance index 0.9 versus 0.63, p < 0.05) (n = 18) was compared to controls (n = 12). PAI-1 was increased (~10-fold, p < 0.001) and had a positive predictive ratio of 6.7. Further, PAI-1 levels correlated to blood oxygen (r = -0.68, p < 0.0001). The plasma's angiogenic potency measured in vitro was associated with umbilical cord blood PAI-1 levels (r = 0.65, p < 0.01). This association was attenuated by PAI-1 inhibiting antibody (p < 0.001). 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.
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Maxim D
authors.initials: MD
authors.lastname: Seferovic
authors.affiliation: Children's Health Research Institute, Departments of Biochemistry and Pediatrics, University of Western Ontario, London, ON, Canada N6C 2V5.
authors.forename: Madhulika B
authors.initials: MB
authors.lastname: Gupta
mesh_terms: D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005317:Fetal Growth Retardation / Q000209:etiology* / Q000378:metabolism; D005311:Fetal Hypoxia / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic / Q000209:etiology* / Q000378:metabolism; D010927:Placental Insufficiency / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011247:Pregnancy; D015854:Up-Regulation
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human