{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:35:52Z","timestamp":1790516152422,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pulmonary artery pressure, vascular remodeling, and ultimately right ventricular heart failure. PAH can have a genetic component (heritable PAH), most often through mutations of bone morphogenetic protein receptor 2, and idiopathic and associated forms. Heritable PAH is not completely penetrant within families, with approximately 20% concurrence of inactivating bone morphogenetic protein receptor 2 mutations and delayed onset of PAH disease. Because one of the treatment options is using prostacyclin analogs, we hypothesized that prostacyclin synthase promoter sequence variants associated with increased mRNA expression may play a protective role in the bone morphogenetic protein receptor 2 unaffected carriers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To characterize the range of prostacyclin synthase promoter variants and assess their transcriptional activities in PAH-relevant cell types. To determine the distribution of prostacyclin synthase promoter variants in PAH, unaffected carriers in heritable PAH families, and control populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Polymerase chain reaction approaches were used to genotype prostacyclin synthase promoter variants in more than 300 individuals. Prostacyclin synthase promoter haplotypes\u2019 transcriptional activities were determined with luciferase reporter assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>We identified a comprehensive set of prostacyclin synthase promoter variants and tested their transcriptional activities in PAH-relevant cell types. We demonstrated differences of prostacyclin synthase promoter activities dependent on their haplotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Prostacyclin synthase promoter sequence variants exhibit a range of transcriptional activities. We discovered a significant bias for more active prostacyclin synthase promoter variants in unaffected carriers as compared with affected patients with PAH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201309-1697oc","type":"journal-article","created":{"date-parts":[[2014,3,7]],"date-time":"2014-03-07T11:14:52Z","timestamp":1394190892000},"page":"1110-1120","source":"Crossref","is-referenced-by-count":19,"title":["Functional Prostacyclin Synthase Promoter Polymorphisms. Impact in Pulmonary Arterial Hypertension"],"prefix":"10.1093","volume":"189","author":[{"given":"Robert S.","family":"Stearman","sequence":"first","affiliation":[{"name":"Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber R.","family":"Cornelius","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Conklin","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Del Rosario","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita M.","family":"Lowe","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihret T.","family":"Elos","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynsey M.","family":"Fettig","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall E.","family":"Wong","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes, Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Hara","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes, Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy D.","family":"Cogan","sequence":"additional","affiliation":[{"name":"Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"John A.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomic Medicine, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Adult Clinical Genetics, Department of Medicine, University of Colorado Denver, School of Medicine, Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian B.","family":"Graham","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rubin M.","family":"Tuder","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Loyd","sequence":"additional","affiliation":[{"name":"Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W.","family":"Geraci","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, School of Medicine, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,5,1]]},"reference":[{"key":"2026032100410530600_bib1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1183\/09059180.00004812","article-title":"Pathways in pulmonary arterial hypertension: the future is here","volume":"21","author":"Sitbon","year":"2012","journal-title":"Eur Respir Rev"},{"key":"2026032100410530600_bib2","doi-asserted-by":"crossref","first-page":"1A","DOI":"10.1016\/j.amjcard.2012.12.002","article-title":"Pulmonary arterial hypertension: new insights into the optimal role of current and emerging prostacyclin therapies","volume":"111","author":"Waxman","year":"2013","journal-title":"Am J Cardiol"},{"key":"2026032100410530600_bib3","author":"U.S. National Library of Medicine. 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