title: Alterations in expression of elastogenic and angiogenic genes by different conditions of mechanical ventilation in newborn rat lung.
abstract: Mechanical ventilation is an important risk factor for development of bronchopulmonary dysplasia. Here we investigated the effects of different tidal volumes (VT) and duration of ventilation on expression of genes involved in alveolarization [tropoelastin (Eln), lysyloxidase-like 1 (Loxl1), fibulin5 (Fbln5), and tenascin-C (Tnc)] and angiogenesis [platelet derived growth factors (Pdgf) and vascular endothelial growth factors (Vegf) and their receptors] in 8-day-old rats. First, pups were ventilated for 8 h with low (LVT: 3.5 ml/kg), moderate (MVT: 8.5 ml/kg), or high (HVT: 25 ml/kg) tidal volumes. LVT and MVT decreased Tnc expression, whereas HVT increased expression of all three elastogenic genes and Tnc. PDGF α-receptor mRNA was increased in all ventilation groups, while Pdgfb expression was decreased after MVT and HVT ventilation. Only HVT ventilation upregulated Vegf expression. Independent of VT, ventilation upregulated Vegfr1 expression, while MVT and HVT downregulated Vegfr2 expression. Next, we evaluated duration (0-24 h) of MVT ventilation on gene expression. Although expression of all elastogenic genes peaked at 12 h of ventilation, only Fbln5 was negatively affected at 24 h. Tnc expression decreased with duration of ventilation. Changes in expression of Pdgfr and Vegfr were maximal at 8 h of ventilation. Disturbed elastin fiber deposition and decrease in small vessel density was only observed after 24 h. Thus, an imbalance between Fbln5 and Eln expression may trigger dysregulated elastin fiber deposition during the first 24 h of mechanical ventilation. Furthermore, ventilation-induced alterations in Pdgf and Vegf receptor expression are tidal volume dependent and may affect pulmonary vessel formation.
authors.affiliation: Physiology and Experimental Medicine Program, Hospital for Sick Children Research Institute, Toronto, Canada; Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, the Netherlands.
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Kroon
authors.affiliation: Physiology and Experimental Medicine Program, Hospital for Sick Children Research Institute, Toronto, Canada;
authors.forename: Jinxia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Physiology and Experimental Medicine Program, Hospital for Sick Children Research Institute, Toronto, Canada; Department of Pediatrics University of Toronto, Toronto, Canada; Department of Physiology, University of Toronto, Toronto, Canada; and martin.post@sickkids.ca.
authors.forename: Martin
authors.initials: M
authors.lastname: Post
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D053898:Biosynthetic Pathways; D001997:Bronchopulmonary Dysplasia / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D004549:Elastin / Q000096:biosynthesis; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D018919:Neovascularization, Physiologic / Q000235:genetics; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012121:Respiration, Artificial / Q000009:adverse effects*; D019063:Tenascin / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D016326:Extracellular Matrix Proteins; C492372:Fbln5 protein, rat; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D019063:Tenascin; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D004549:Elastin; D000594:Amino Acid Oxidoreductases; C574516:LOXL1 protein, rat
keywords: PDGF; VEGF; elastin; fibulin5; mechanical ventilation; tenascin-C