{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T23:10:02Z","timestamp":1741907402564,"version":"3.38.0"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T00:00:00Z","timestamp":1309478400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL066012","HL098053","DK083506"],"award-info":[{"award-number":["HL066012","HL098053","DK083506"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008522","name":"University of Illinois at Chicago","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008522","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Pulm. circ."],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:p>Fenfluramine is prescribed either alone or in combination with phentermine as part of Fen\u2010Phen, an anti\u2010obesity medication. Fenfluramine was withdrawn from the US market in 1997 due to reports of heart valvular disease, pulmonary arterial hypertension, and cardiac fibrosis. Particularly, idiopathic pulmonary arterial hypertension (IPAH), previously referred to as primary pulmonary hypertension (PPH), was found to be associated with the use of Fen\u2010Phen, fenfluramine, and fenfluramine derivatives. The underlying mechanism of fenfluramine\u2010associated pulmonary hypertension is still largely unknown. We reasoned that investigating drug\u2010induced gene dysregulation would enhance our understanding of the fenfluramine\u2010associated pathogenic mechanism of IPAH. Whole\u2010genome gene expression profiles in fenfluramine\u2010treated human pulmonary artery smooth muscle (PASMC) and endothelial (PAEC) cells (isolated from normal subjects) were compared with baseline expression in untreated cells. Fenfluramine treatment caused dysregulation in a substantial number of genes involved in a variety of pathways and biological processes. In addition to several common pathways and biological processes such as \u201cMAPK signaling pathway,\u201d \u201cinflammation response,\u201d and \u201ccalcium signaling pathway\u201d shared between both cell types, pathways and biological processes such as \u201cblood circulation,\u201d \u201cmuscle system process,\u201d and \u201cimmune response\u201d were enriched among the dysregulated genes in PASMC. Pathways and biological processes such as those related to cell cycle, however, were enriched among the dysregulated genes in PAEC, indicating that fenfluramine could affect unique pathways (or differentially) in different types of pulmonary artery cells. While awaiting validation in a larger cohort, these results strongly suggested that fenfluramine could induce significant dysregulation of genes in multiple biological processes and pathways critical for normal pulmonary vascular functions and structure. The transcriptional and posttranscriptional changes in these genes may, therefore, contribute to the pathogenesis of fenfluramine\u2010associated IPAH.<\/jats:p>","DOI":"10.4103\/2045-8932.87310","type":"journal-article","created":{"date-parts":[[2011,11,9]],"date-time":"2011-11-09T10:46:04Z","timestamp":1320835564000},"page":"405-418","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Fenfluramine\u2010Induced Gene Dysregulation in Human Pulmonary Artery Smooth Muscle and Endothelial Cells"],"prefix":"10.1002","volume":"1","author":[{"given":"Weijuan","family":"Yao","sequence":"first","affiliation":[{"name":"Department of Medicine University of California San Diego La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbo","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Illinois at Chicago Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Zeifman","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Illinois at Chicago Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Lofti","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences institute for Personalized Respiratory Medicine University of Illinois at Chicago Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmelle V.","family":"Remillard","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California San Diego La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayako","family":"Makino","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California San Diego La Jolla California USA"},{"name":"Department of Medicine University of Illinois at Chicago Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David L.","family":"Perkins","sequence":"additional","affiliation":[{"name":"Department of Medicine University of California San Diego La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joe G. N.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Illinois at Chicago Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason X. 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