|Sen, Partha -|
|Choudhury, Tiyashi -|
|Smith, E. O'Brian -|
|Langston, Claire -|
Submitted to: Electronic Publication
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 13, 2010
Publication Date: March 23, 2010
Citation: Sen, P., Choudhury, T., Smith, E., Langston, C. 2010. Expression of angiogenic and vasculogenic proteins in the lung in alveolar capillary dysplasia/misalignment of pulmonary veins: an immunohistochemical study. Pediatric and Developmental Pathology. 13:354-361. Interpretive Summary: The paper describes the expression of eight proteins that are involved in blood vessel formation in the lungs of patients with Alveolar Capillary Dysplasia with Misalignment of Veins (ACD/MPV), a deadly disorder of the newborn lung. The major characteristics of this disorder are misalignment of pulmonary veins, thickening of pulmonary arteries, lobular underdevelopment, thickening of the alveolar wall and a severe lack of capillaries. The disease does not have a gender bias and is uniformly lethal. The proteins studied were endothelial nitric oxide synthase-3 (NOS3), fetal liver kinase 1 (flk1), hypoxia inducible factor 1' (IHF') von Hippel Lindau protein (VHLP) and three isoforms of vascular endothelial growth factors (VEGF147, VEGFC1 and VEGFA20). Statistical analysis of the data revealed significant differences in the degree of expression between ACD/MPV and control lung. This study does not clearly implicate a genetic abnormality of the disorder.
Technical Abstract: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare, universally fatal developmental disorder of the lung affecting both the parenchyma and the vasculature. Its cause remains incompletely understood; the occurrence of familial cases has suggested a genetic abnormality. While several candidate genes have been studied previously, the affected pathway(s) have not yet been fully defined. The expression patterns of 8 gene products (endothelial nitric oxide synthase-3, fetal liver kinase-1, hypoxia inducible factor 1a, Von Hippel Lindau protein, 3 vascular endothelial growth factors [VEGF147, VEGFC1, and VEGFA20], and activin receptor-like kinase 1), all known to have a role in vascular development in the lung, were studied in 13 ACD/MPV and 17 control lungs by immunohistochemistry to further address the underlying molecular abnormality. Expression was graded with regard to degree and extent for multiple components of the lung parenchyma and pulmonary vasculature for each antibody. Statistical analyses of the data using the Mann-Whitney test revealed only a few significant differences (P = 0.05) in degree of expression between ACD/MPV and control lung samples and do not clearly implicate one of these genes in ACD/MPV.