| Defective angiogenesis in hypoplastic human fetal lungs correlates with nitric oxide synthase deficiency that occurs despite enhanced angiopoietin-2 and VEGF. | |
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MedLine Citation:
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PMID: 20348277 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Lung hypoplasia (LH) is a life-threatening congenital abnormality with various causes. It involves vascular bed underdevelopment with abnormal arterial muscularization leading to pulmonary hypertension. Because underlying molecular changes are imperfectly known and sometimes controversial, we determined key factors of angiogenesis along intrauterine development, focusing at the angiopoietin (ANG)/Tie-2 system. Lung specimens from medical terminations of pregnancy (9-37 wk) were used, including LH due to congenital diaphragmatic hernia (CDH) or other causes, and nonpulmonary disease samples were used as controls. ELISA determination indicated little ANG-1 change during pregnancy and no effect of LH, whereas Tie-2 declined similarly between 9 and 37 wk in LH and controls. By contrast, ANG-2 markedly increased in LH from 24 wk, whereas it remained stable in controls. Because VEGF increased also, this was interpreted as an attempt to overcome vascular underdevelopment. Hypothesizing that its inefficiency might be due to impaired downstream mechanism, endothelial nitric oxide synthase (eNOS) was determined by semiquantitative Western blot and found to be reduced by approximately 75%, mostly in the instance of CDH. In conclusion, angiogenesis remains defective in hypoplastic lungs despite reactive enhancement of VEGF and ANG-2 production, which could be due, at least in part, to insufficient eNOS expression. |
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Authors:
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Olivier Boucherat; Marie-Laure Franco-Montoya; Christophe Delacourt; Jelena Martinovic; Virginie Masse; Caroline Elie; Bernard Thébaud; Alexandra Benachi; Jacques R Bourbon |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-26 |
Journal Detail:
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Title: American journal of physiology. Lung cellular and molecular physiology Volume: 298 ISSN: 1522-1504 ISO Abbreviation: Am. J. Physiol. Lung Cell Mol. Physiol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-20 Completed Date: 2010-06-14 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 100901229 Medline TA: Am J Physiol Lung Cell Mol Physiol Country: United States |
Other Details:
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Languages: eng Pagination: L849-56 Citation Subset: IM |
Affiliation:
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Institut Mondor de Recherche Biomédicale, Institut National de Santé et de Recherche Médicale Unité 955, Créteil, France. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiopoietin-1
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metabolism Angiopoietin-2 / metabolism* Female Humans Hypertension, Pulmonary Lung / abnormalities, blood supply*, embryology Neovascularization, Pathologic / physiopathology Nitric Oxide Synthase Type III / deficiency* Pregnancy Receptor, TIE-2 / metabolism Vascular Endothelial Growth Factor A / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Angiopoietin-1; 0/Angiopoietin-2; 0/Vascular Endothelial Growth Factor A; EC 1.14.13.39/NOS3 protein, human; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 2.7.10.1/Receptor, TIE-2 |
| Comments/Corrections | |
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