{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T13:18:26Z","timestamp":1781702306679,"version":"3.54.5"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,2,1]],"date-time":"2020-02-01T00:00:00Z","timestamp":1580515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Translational research is essential to the development of reverse-remodeling strategies for the treatment of pulmonary vascular disease, pulmonary hypertension, and heart failure via mechanistic in vivo studies using animal models resembling human pulmonary arterial hypertension (PAH), cardiovascular remodeling, and progressive right heart failure. Since 2007, peroxisome proliferator\u2013activated receptor \u03b3 (PPAR\u03b3) agonists have emerged as promising novel, antiproliferative, antiinflammatory, insulin-sensitizing, efficient medications for the treatment of PAH. However, early diabetes study results, their subsequent misinterpretations, errors in published review articles, and rumors regarding potential adverse effects in the literature have dampened enthusiasm for considering pharmacological PPAR\u03b3 activation for the treatment of cardiovascular diseases, including PAH. Most recently, the thiazolidinedione class PPAR\u03b3 agonist pioglitazone underwent a clinical revival, especially based on the IRIS (Insulin Resistance Intervention After Stroke) study, a randomized controlled trial in 3,876 patients without diabetes status post\u2013transient ischemic attack\/ischemic stroke who were clinically followed for 4.8 years. We discuss preclinical basic translational findings and randomized controlled trials related to the beneficial and adverse effects of PPAR\u03b3 agonists of the thiazolidinedione class, with a particular focus on the last 5 years. The objective is a data-driven approach to set the preclinical and clinical study record straight. The convincing recent clinical trial data on the lack of significant toxicity in high-risk populations justify the timely conduct of clinical studies to achieve \u201crepurposing\u201d or \u201crepositioning\u201d of pioglitazone for the treatment of clinical PAH.<\/jats:p>","DOI":"10.1165\/rcmb.2019-0226ps","type":"journal-article","created":{"date-parts":[[2019,10,2]],"date-time":"2019-10-02T12:38:42Z","timestamp":1570019922000},"page":"143-156","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":37,"title":["Activation of the Metabolic Master Regulator PPAR\u03b3: A Potential PIOneering Therapy for Pulmonary Arterial Hypertension"],"prefix":"10.1093","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0709-3935","authenticated-orcid":false,"given":"Georg","family":"Hansmann","sequence":"first","affiliation":[{"name":"Department of Pediatric Cardiology and Critical Care, Hannover Medical School, Hannover, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6437-2119","authenticated-orcid":false,"given":"Laurent","family":"Calvier","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology and Critical Care, Hannover Medical School, Hannover, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3334-7046","authenticated-orcid":false,"given":"Michael G.","family":"Risbano","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine"},{"name":"Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9520-7527","authenticated-orcid":false,"given":"Stephen Y.","family":"Chan","sequence":"additional","affiliation":[{"name":"Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, and"},{"name":"Division of Cardiology, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,2,1]]},"reference":[{"key":"2026021100413348500_bib1","doi-asserted-by":"crossref","first-page":"1801889","DOI":"10.1183\/13993003.01889-2018","article-title":"Risk stratification and medical therapy of pulmonary arterial hypertension","volume":"53","author":"Gali\u00e8","year":"2019","journal-title":"Eur Respir J"},{"key":"2026021100413348500_bib2","doi-asserted-by":"crossref","first-page":"1801887","DOI":"10.1183\/13993003.01887-2018","article-title":"Pathology and pathobiology of pulmonary hypertension: state of the art and research perspectives","volume":"53","author":"Humbert","year":"2019","journal-title":"Eur Respir 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