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Genomewide RNA expression profiling in lung identifies distinct signatures in idiopathic pulmonary arterial hypertension and secondary pulmonary hypertension
Journal article   Open access   Peer reviewed

Genomewide RNA expression profiling in lung identifies distinct signatures in idiopathic pulmonary arterial hypertension and secondary pulmonary hypertension

Revathi Rajkumar, Kazuhisa Konishi, Thomas J Richards, David C Ishizawar, Andrew C Wiechert, Naftali Kaminski and Ferhaan Ahmad
American journal of physiology. Heart and circulatory physiology, Vol.298(4), pp.H1235-1248
04/2010
DOI: 10.1152/ajpheart.00254.2009
PMCID: PMC2853417
PMID: 20081107
url
https://doi.org/10.1152/ajpheart.00254.2009View
Published (Version of record) Open Access

Abstract

Idiopathic pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by pulmonary arteriolar remodeling. This investigation aimed to identify genes involved specifically in the pathogenesis of PAH and not other forms of pulmonary hypertension (PH). Using genomewide microarray analysis, we generated the largest data set to date of RNA expression profiles from lung tissue specimens from 1) 18 PAH subjects and 2) 8 subjects with PH secondary to idiopathic pulmonary fibrosis (IPF) and 3) 13 normal subjects. A molecular signature of 4,734 genes discriminated among these three cohorts. We identified significant novel biological changes that were likely to contribute to the pathogenesis of PAH, including regulation of actin-based motility, protein ubiquitination, and cAMP, transforming growth factor-beta, MAPK, estrogen receptor, nitric oxide, and PDGF signaling. Bone morphogenic protein receptor type II expression was downregulated, even in subjects without a mutation in this gene. Women with PAH had higher expression levels of estrogen receptor 1 than normal women. Real-time quantitative PCR confirmed differential expression of the following genes in PAH relative to both normal controls and PH secondary to IPF: a disintegrin-like and metalloprotease with thrombospondin type 1 motif 9, cell adhesion molecule with homology to L1CAM, cytochrome b(558) and beta-polypeptide, coagulation factor II receptor-like 3, A-myb myeloblastosis viral oncogene homolog 1, nuclear receptor coactivator 2, purinergic receptor P2Y, platelet factor 4, phospholamban, and tropomodulin 3. This study shows that PAH and PH secondary to IPF are characterized by distinct gene expression signatures, implying distinct pathophysiological mechanisms.
 Lung - pathology Bone Morphogenetic Protein Receptors, Type II - genetics Humans Middle Aged Male Gene Expression Profiling Hypertension, Pulmonary - metabolism Bone Morphogenetic Protein Receptors, Type II - metabolism Case-Control Studies Genome, Human - genetics RNA - genetics Estrogen Receptor alpha - genetics Adult Estrogen Receptor alpha - metabolism Female Signal Transduction - physiology Aged Idiopathic Pulmonary Fibrosis - complications Lung - metabolism Hypertension, Pulmonary - etiology Hypertension, Pulmonary - pathology RNA - metabolism

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