RATIONALE: Preterm infants exposed to mechanical ventilation and oxygen are at risk for bronchopulmonary dysplasia (BPD), a multifactorial chronic lung disorder characterized by arrested alveolar development. Studies have described disruption of microvascular development in BPD, characterized by primitive angioarchitectural patterns reminiscent of the canalicular/saccular stages of lung development. The molecular regulation of this BPD-associated dysangiogenesis remains undetermined. OBJECTIVES: Endoglin (CD105), a hypoxia-inducible transforming growth factor-beta coreceptor, has been implicated as an important regulator of angiogenesis in various neoplastic and nonneoplastic conditions. The aim of this study was to investigate the expression of endoglin and other angiogenesis-related factors in ventilated preterm human lungs. METHODS: We have studied endoglin protein and mRNA expression in postmortem lungs of short-term and long-term ventilated preterm infants. Control subjects were age-matched infants who had lived for less than 1 hour. MEASUREMENTS AND MAIN RESULTS: Lungs of short-term ventilated preterm infants showed significant upregulation of endoglin mRNA and protein levels, immunolocalized to the microvasculature. Similar but more variable endoglin upregulation was noted in lungs of long-term ventilated infants with BPD. The mRNA levels of vascular endothelial growth factor, angiopoietin-1, and their respective receptors were significantly lower in ventilated lungs than in age-matched nonventilated control lungs. CONCLUSIONS: BPD is associated with a shift from traditional angiogenic growth factors (vascular endothelial growth factor, angiopoietin-1) to alternative regulators such as endoglin, which may contribute to BPD-associated microvascular dysangiogenesis.
RATIONALE: Preterm infants exposed to mechanical ventilation and oxygen are at risk for bronchopulmonary dysplasia (BPD), a multifactorial chronic lung disorder characterized by arrested alveolar development. Studies have described disruption of microvascular development in BPD, characterized by primitive angioarchitectural patterns reminiscent of the canalicular/saccular stages of lung development. The molecular regulation of this BPD-associated dysangiogenesis remains undetermined. OBJECTIVES:Endoglin (CD105), a hypoxia-inducible transforming growth factor-beta coreceptor, has been implicated as an important regulator of angiogenesis in various neoplastic and nonneoplastic conditions. The aim of this study was to investigate the expression of endoglin and other angiogenesis-related factors in ventilated preterm human lungs. METHODS: We have studied endoglin protein and mRNA expression in postmortem lungs of short-term and long-term ventilated preterm infants. Control subjects were age-matched infants who had lived for less than 1 hour. MEASUREMENTS AND MAIN RESULTS: Lungs of short-term ventilated preterm infants showed significant upregulation of endoglin mRNA and protein levels, immunolocalized to the microvasculature. Similar but more variable endoglin upregulation was noted in lungs of long-term ventilated infants with BPD. The mRNA levels of vascular endothelial growth factor, angiopoietin-1, and their respective receptors were significantly lower in ventilated lungs than in age-matched nonventilated control lungs. CONCLUSIONS: BPD is associated with a shift from traditional angiogenic growth factors (vascular endothelial growth factor, angiopoietin-1) to alternative regulators such as endoglin, which may contribute to BPD-associated microvascular dysangiogenesis.
Authors: H M Arthur; J Ure; A J Smith; G Renforth; D I Wilson; E Torsney; R Charlton; D V Parums; T Jowett; D A Marchuk; J Burn; A G Diamond Journal: Dev Biol Date: 2000-01-01 Impact factor: 3.582
Authors: M Guerrero-Esteo; P Lastres; A Letamendía; M J Pérez-Alvarez; C Langa; L A López; A Fabra; A García-Pardo; S Vera; M Letarte; C Bernabéu Journal: Eur J Cell Biol Date: 1999-09 Impact factor: 4.492
Authors: J A Lemons; C R Bauer; W Oh; S B Korones; L A Papile; B J Stoll; J Verter; M Temprosa; L L Wright; R A Ehrenkranz; A A Fanaroff; A Stark; W Carlo; J E Tyson; E F Donovan; S Shankaran; D K Stevenson Journal: Pediatrics Date: 2001-01 Impact factor: 7.124
Authors: M Jakkula; T D Le Cras; S Gebb; K P Hirth; R M Tuder; N F Voelkel; S H Abman Journal: Am J Physiol Lung Cell Mol Physiol Date: 2000-09 Impact factor: 5.464
Authors: P Lastres; T Bellon; C Cabañas; F Sanchez-Madrid; A Acevedo; A Gougos; M Letarte; C Bernabeu Journal: Eur J Immunol Date: 1992-02 Impact factor: 5.532
Authors: Bernard Thébaud; Kara N Goss; Matthew Laughon; Jeffrey A Whitsett; Steven H Abman; Robin H Steinhorn; Judy L Aschner; Peter G Davis; Sharon A McGrath-Morrow; Roger F Soll; Alan H Jobe Journal: Nat Rev Dis Primers Date: 2019-11-14 Impact factor: 52.329
Authors: Lucia M Mokres; Kakoli Parai; Anne Hilgendorff; Robert Ertsey; Cristina M Alvira; Marlene Rabinovitch; Richard D Bland Journal: Am J Physiol Lung Cell Mol Physiol Date: 2009-10-23 Impact factor: 5.464