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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-\u03b2, 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<jats:sub>558<\/jats:sub>and \u03b2-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.<\/jats:p>","DOI":"10.1152\/ajpheart.00254.2009","type":"journal-article","created":{"date-parts":[[2010,1,16]],"date-time":"2010-01-16T03:06:34Z","timestamp":1263611194000},"page":"H1235-H1248","source":"Crossref","is-referenced-by-count":182,"title":["Genomewide RNA expression profiling in lung identifies distinct signatures in idiopathic pulmonary arterial hypertension and secondary pulmonary hypertension"],"prefix":"10.1152","volume":"298","author":[{"given":"Revathi","family":"Rajkumar","sequence":"first","affiliation":[{"name":"Cardiovascular Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhisa","family":"Konishi","sequence":"additional","affiliation":[{"name":"Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Richards","sequence":"additional","affiliation":[{"name":"Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Ishizawar","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Wiechert","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naftali","family":"Kaminski","sequence":"additional","affiliation":[{"name":"Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, and"},{"name":"Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferhaan","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute and"},{"name":"Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002642"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/embo-reports\/kvf057"},{"key":"B3","doi-asserted-by":"crossref","unstructured":"Aldred MA, Vijayakrishnan J, James V, Soubrier F, Gomez-Sanchez MA, Martensson G, Galie N, Manes A, Corris P, Simonneau G, Humbert M, Morrell NW, Trembath RC. 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