Expression of angiogenesis-related factors in lungs of patients with congenital diaphragmatic hernia and pulmonary hypoplasia of other causes

Congenital diaphragmatic hernia (CDH) is a congenital disorder, complicated by pulmonary hypoplasia (PH) and pulmonary hypertension. Hypoplastic lungs have fewer and smaller airspaces than normal, with thicker interalveolar septa; the adventitia and media of pulmonary arteries are thickened, and the total size of the pulmonary vascular bed is decreased compared to normal. Although histological abnormalities in PH have been described, less is known about the underlying molecular mechanisms. Therefore, we have investigated a series of proteins, known to be involved in angiogenesis, including von Hippel-Lindau protein (pVHL), hypoxia-inducible factor-1a (HIF-1a), vascular endothelial growth factor (VEGF), fetal liver kinase 1 (Flk-1), and endothelial and inducible nitric oxide synthase (eNOS, iNOS) by immunohistochemistry on paraffin-embedded lung tissue of CDH patients (n = 13), patients with lung hypoplasia due to other causes (n = 20), and normal controls (n = 33). pVHL was expressed more frequently in the arterial smooth muscle cells of CDH lungs compared with both other groups. Furthermore, HIF-1a was expressed less frequently in the endothelium of arteries, veins, and capillaries of CDH lungs as compared with both other groups. No differences were observed in the expression patterns of VEGF, Flk-1, eNOS, and iNOS between the different groups. Our data suggest a role for pVHL and HIF-1a in normal and abnormal pulmonary angiogenesis. The differential expression of these proteins may provide a molecular basis for the histological differences observed in the lung vessels of patients with CDH

Defective angiogenesis in hypoplastic human fetal lungs correlates with nitric oxide synthase deficiency that occurs despite enhanced angiopoietin-2 and VEGF.

International audienceLung 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

Aumento da transparência pulmonar na infância: ensaio iconográfico Increased radiolucency of the lungs in infancy: iconographic essay

Assimetrias torácicas representadas pelo aumento da transparência pulmonar são causas importantes de morbidade na população pediátrica. A avaliação dos pacientes afetados freqüentemente requer múltiplas modalidades de imagem para diagnosticar a anomalia e planejar a correção cirúrgica. Os autores analisam e ilustram os aspectos de assimetrias torácicas comuns e raras, com ênfase nas manifestações radiológicas. A aplicabilidade das diversas modalidades de imagem no diagnóstico e tratamento é avaliada. Diagnósticos diferenciais, assim como armadilhas e dificuldades diagnósticas, são incluídas.<br>Thoracic asymmetries characterized by increased radiolucency of the lungs are important causes of morbidity in infants and children. Evaluation of affected patients frequently requires multiple imaging methods to diagnose the abnormality and to plan the surgical correction. The authors review and illustrate the characteristics of both common and rare thoracic asymmetries with emphasis on the radiological findings. The usefulness of different imaging methods in the diagnosis and treatment of these conditions is evaluated. The differential diagnosis as well the pitfalls and diagnostic difficulties are also discussed