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Long non\u2010coding RNAs (lncRNAs) are key regulators of cellular function. Using a compartment\u2010specific transcriptional profiling approach, we sought to investigate the link between transcriptional reprogramming by lncRNAs and the maladaptive smooth muscle cell phenotype in IPAH. Transcriptional profiling of small remodelled arteries from 18 IPAH patients and 17 controls revealed global perturbations in metabolic, neuronal, proliferative, and immunological processes. We demonstrated an IPAH\u2010specific lncRNA expression profile and identified the lncRNA <jats:italic>PAXIP1\u2010AS1<\/jats:italic> as highly abundant. Comparative transcriptomic analysis and functional assays revealed an intrinsic role for <jats:italic>PAXIP1\u2010AS1<\/jats:italic> in orchestrating the hyperproliferative and migratory actions of IPAH smooth muscle cells. Further, we showed that <jats:italic>PAXIP1\u2010AS1<\/jats:italic> mechanistically interferes with the focal adhesion axis via regulation of expression and phosphorylation of its downstream target paxillin. Overall, we show that changes in the lncRNA transcriptome contribute to the disease\u2010specific transcriptional landscape in IPAH. Our results suggest that lncRNAs, such as <jats:italic>PAXIP1\u2010AS1<\/jats:italic>, can modulate smooth muscle cell function by affecting multiple IPAH\u2010specific transcriptional programmes. \u00a9 2018 The Authors. <jats:italic>The Journal of Pathology published<\/jats:italic> by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.5195","type":"journal-article","created":{"date-parts":[[2018,11,19]],"date-time":"2018-11-19T02:50:35Z","timestamp":1542595835000},"page":"357-370","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Long non\u2010coding RNAs influence the transcriptome in pulmonary arterial hypertension: the role of <i>PAXIP1\u2010AS1<\/i>"],"prefix":"10.1002","volume":"247","author":[{"given":"Katharina","family":"Jandl","sequence":"first","affiliation":[{"name":"Ludwig Boltzmann Institute for Lung Vascular Research  Graz 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