BACKGROUND: Among preterm infants, respiratory distress syndrome (RDS) is characterized by the presence of intraalveolar fibrin deposition. Fibrin monomers inhibit surfactant function effectively. However, little is known about potential disturbances of intraalveolar fibrinolysis in RDS. We studied levels of major plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA) in lungs of preterm infants with RDS. METHODS: The antigen levels of PAI-1, tPA, and uPA were measured in 262 samples of tracheal aspirate fluid collected from 37 intubated preterm infants during the first 2 postnatal weeks. To examine the expression of PAI-1, tPA, and uPA in lung tissue, immunohistochemical analyses were performed on autopsy specimens from 7 preterm infants with RDS and 6 newborn infants without pulmonary pathologic conditions. RESULTS: For infants with an immature surfactant profile, as indicated by lecithin/sphingomyelin ratios in tracheal aspirate fluid of < 10, PAI-1 levels and ratios of PAI-1 to uPA and tPA were significantly higher during postnatal days 1 to 2, compared with infants with lecithin/sphingomyelin ratios of > or = 10. Moreover, infants who subsequently developed bronchopulmonary dysplasia (BPD) (n = 15) had higher PAI-1 levels on days 3 to 4 and days 7 to 8 than did those who survived without BPD. For preterm infants with RDS, immunohistochemical analyses demonstrated increased expression of PAI-1, tPA, and uPA predominantly in alveolar epithelium. CONCLUSIONS: High concentrations of PAI-1 and an increased ratio of PAI-1 to uPA, with a concurrently less-increased ratio of PAI-1 to tPA, are associated with the severity of RDS among preterm infants during the first postnatal days. Pulmonary inhibition of fibrinolysis is a pathophysiologic feature of RDS and may play a role in the development of BPD.
BACKGROUND: Among preterm infants, respiratory distress syndrome (RDS) is characterized by the presence of intraalveolar fibrin deposition. Fibrin monomers inhibit surfactant function effectively. However, little is known about potential disturbances of intraalveolar fibrinolysis in RDS. We studied levels of major plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA) in lungs of preterm infants with RDS. METHODS: The antigen levels of PAI-1, tPA, and uPA were measured in 262 samples of tracheal aspirate fluid collected from 37 intubated preterm infants during the first 2 postnatal weeks. To examine the expression of PAI-1, tPA, and uPA in lung tissue, immunohistochemical analyses were performed on autopsy specimens from 7 preterm infants with RDS and 6 newborn infants without pulmonary pathologic conditions. RESULTS: For infants with an immature surfactant profile, as indicated by lecithin/sphingomyelin ratios in tracheal aspirate fluid of < 10, PAI-1 levels and ratios of PAI-1 to uPA and tPA were significantly higher during postnatal days 1 to 2, compared with infants with lecithin/sphingomyelin ratios of > or = 10. Moreover, infants who subsequently developed bronchopulmonary dysplasia (BPD) (n = 15) had higher PAI-1 levels on days 3 to 4 and days 7 to 8 than did those who survived without BPD. For preterm infants with RDS, immunohistochemical analyses demonstrated increased expression of PAI-1, tPA, and uPA predominantly in alveolar epithelium. CONCLUSIONS: High concentrations of PAI-1 and an increased ratio of PAI-1 to uPA, with a concurrently less-increased ratio of PAI-1 to tPA, are associated with the severity of RDS among preterm infants during the first postnatal days. Pulmonary inhibition of fibrinolysis is a pathophysiologic feature of RDS and may play a role in the development of BPD.
Authors: Alvin T Kho; Divya Chhabra; Sunita Sharma; Weiliang Qiu; Vincent J Carey; Roger Gaedigk; Carrie A Vyhlidal; J Steven Leeder; Kelan G Tantisira; Scott T Weiss Journal: Am J Respir Cell Mol Biol Date: 2016-06 Impact factor: 6.914
Authors: Cherie D Foster; Linda S Varghese; Rachel B Skalina; Linda W Gonzales; Susan H Guttentag Journal: Pediatr Res Date: 2007-04 Impact factor: 3.756
Authors: Cagatay Karaaslan; Hiroshi Hirakawa; Ryuji Yasumatsu; Ling-Yi L Chang; Richard A Pierce; James D Crapo; Sule Cataltepe Journal: Pediatr Res Date: 2011-10 Impact factor: 3.756
Authors: Victoria E Jackson; Jeanne C Latourelle; Louise V Wain; Albert V Smith; Megan L Grove; Traci M Bartz; Ma'en Obeidat; Michael A Province; Wei Gao; Beenish Qaiser; David J Porteous; Patricia A Cassano; Tarunveer S Ahluwalia; Niels Grarup; Jin Li; Elisabeth Altmaier; Jonathan Marten; Sarah E Harris; Ani Manichaikul; Tess D Pottinger; Ruifang Li-Gao; Allan Lind-Thomsen; Anubha Mahajan; Lies Lahousse; Medea Imboden; Alexander Teumer; Bram Prins; Leo-Pekka Lyytikäinen; Gudny Eiriksdottir; Nora Franceschini; Colleen M Sitlani; Jennifer A Brody; Yohan Bossé; Wim Timens; Aldi Kraja; Anu Loukola; Wenbo Tang; Yongmei Liu; Jette Bork-Jensen; Johanne M Justesen; Allan Linneberg; Leslie A Lange; Rajesh Rawal; Stefan Karrasch; Jennifer E Huffman; Blair H Smith; Gail Davies; Kristin M Burkart; Josyf C Mychaleckyj; Tobias N Bonten; Stefan Enroth; Lars Lind; Guy G Brusselle; Ashish Kumar; Beate Stubbe; Mika Kähönen; Annah B Wyss; Bruce M Psaty; Susan R Heckbert; Ke Hao; Taina Rantanen; Stephen B Kritchevsky; Kurt Lohman; Tea Skaaby; Charlotta Pisinger; Torben Hansen; Holger Schulz; Ozren Polasek; Archie Campbell; John M Starr; Stephen S Rich; Dennis O Mook-Kanamori; Åsa Johansson; Erik Ingelsson; André G Uitterlinden; Stefan Weiss; Olli T Raitakari; Vilmundur Gudnason; Kari E North; Sina A Gharib; Don D Sin; Kent D Taylor; George T O'Connor; Jaakko Kaprio; Tamara B Harris; Oluf Pederson; Henrik Vestergaard; James G Wilson; Konstantin Strauch; Caroline Hayward; Shona Kerr; Ian J Deary; R Graham Barr; Renée de Mutsert; Ulf Gyllensten; Andrew P Morris; M Arfan Ikram; Nicole Probst-Hensch; Sven Gläser; Eleftheria Zeggini; Terho Lehtimäki; David P Strachan; Josée Dupuis; Alanna C Morrison; Ian P Hall; Martin D Tobin; Stephanie J London Journal: Wellcome Open Res Date: 2018-01-12