Expression of angiogenic and vasculogenic proteins in the lung in alveolar capillary dysplasia/misalignment of pulmonary veins: an immunohistochemical study

Pediatr Dev Pathol. 2010 Sep-Oct;13(5):354-61. doi: 10.2350/09-04-0640-OA.1. Epub 2010 Mar 23.

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 1α, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type II / biosynthesis
  • Gene Expression Profiling
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
  • Immunohistochemistry
  • Infant
  • Infant, Newborn
  • Neovascularization, Pathologic*
  • Nitric Oxide Synthase Type III / biosynthesis
  • Persistent Fetal Circulation Syndrome / metabolism
  • Pulmonary Alveoli / abnormalities
  • Pulmonary Alveoli / metabolism
  • Pulmonary Veins / abnormalities*
  • Pulmonary Veins / metabolism*
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor Receptor-2 / biosynthesis
  • Von Hippel-Lindau Tumor Suppressor Protein / biosynthesis

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Vascular Endothelial Growth Factor Receptor-2
  • ACVRL1 protein, human
  • Activin Receptors, Type II
  • VHL protein, human

Supplementary concepts

  • Alveolar capillary dysplasia