• Partha Sen, Avinash V Dharmadhikari, Tadeusz Majewski, Mahmoud A Mohammad, Tanya V Kalin, Joanna Zabielska, Xiaomeng Ren, Molly Bray, Hannah M Brown, Stephen Welty, Sundararajah Thevananther, Claire Langston, Przemyslaw Szafranski, Monica J Justice, Vladimir V Kalinichenko, Anna Gambin, John Belmont, and Pawel Stankiewicz.
• Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America.
• Plos One. 2014 Jan 1; 9 (4): e94390.

AbstractAlveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV) is a developmental disorder of the lungs, primarily affecting their vasculature. FOXF1 haploinsufficiency due to heterozygous genomic deletions and point mutations have been reported in most patients with ACDMPV. The majority of mice with heterozygous loss-of-function of Foxf1 exhibit neonatal lethality with evidence of pulmonary hemorrhage in some of them. By comparing transcriptomes of human ACDMPV lungs with control lungs using expression arrays, we found that several genes and pathways involved in lung development, angiogenesis, and in pulmonary hypertension development, were deregulated. Similar transcriptional changes were found in lungs of the postnatal day 0.5 Foxf1+/- mice when compared to their wildtype littermate controls; 14 genes, COL15A1, COL18A1, COL6A2, ESM1, FSCN1, GRINA, IGFBP3, IL1B, MALL, NOS3, RASL11B, MATN2, PRKCDBP, and SIRPA, were found common to both ACDMPV and Foxf1 heterozygous lungs. Our results advance knowledge toward understanding of the molecular mechanism of ACDMPV, lung development, and its vasculature pathology. These data may also be useful for understanding etiologies of other lung disorders, e.g. pulmonary hypertension, bronchopulmonary dysplasia, or cancer.

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