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Vascular disease is associated with loss of PPAR\u03b3 in pulmonary microvascular endothelial cells (PMVEC), we evaluated the role of PPAR\u03b3 in PMVEC functions, such as angiogenesis and migration. The role of PPAR\u03b3 in angiogenesis was evaluated in Tie2CrePPAR\u03b3flox\/flox and wild type (WT) mice, and in mouse and human PMVECs. RNA-sequencing and bioinformatic approaches were utilized to reveal angiogenesis-associated targets for PPAR\u03b3. Tie2CrePPAR\u03b3flox\/flox mice showed an impaired angiogenic capacity. Analysis of endothelial progenitor-like cells using bone marrow transplantation combined with evaluation of isolated PMVECs revealed that loss of PPAR\u03b3 attenuates the migration and angiogenic capacity of mature PMVECs. PPAR\u03b3-deficient human PMVECs showed a similar migration defect in culture. Bioinformatic and experimental analyses revealed E2F1 as a novel target of PPAR\u03b3 in the regulation of PMVEC migration. Disruption of the PPAR\u03b3-E2F1 axis was associated with a dysregulated Wnt pathway related to the GSK3\u03b2 interaction protein. In conclusion, PPAR\u03b3 plays an important role in sustaining angiogenic potential in mature PMVECs through E2F1-mediated gene regulation.<\/jats:p>","DOI":"10.1242\/jcs.169011","type":"journal-article","created":{"date-parts":[[2016,1,8]],"date-time":"2016-01-08T03:28:52Z","timestamp":1452223732000},"source":"Crossref","is-referenced-by-count":23,"title":["Loss of PPAR\u03b3 in endothelial cells leads to impaired angiogenesis"],"prefix":"10.1242","author":[{"given":"Sanna","family":"Vattulainen-Collanus","sequence":"first","affiliation":[{"name":"Children's Hospital Helsinki, Pediatric Cardiology, University of Helsinki and Helsinki University Central Hospital, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oyediran","family":"Akinrinade","sequence":"additional","affiliation":[{"name":"Children's Hospital Helsinki, Pediatric Cardiology, University of Helsinki and Helsinki University Central Hospital, Finland"},{"name":"Institute of Biomedicine, University of Helsinki, Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Molong","family":"Li","sequence":"additional","affiliation":[{"name":"The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"},{"name":"Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minna","family":"Koskenvuo","sequence":"additional","affiliation":[{"name":"Children's Hospital Helsinki, Division of Hematology-Oncology and Stem Cell Transplantation, University of Helsinki and Helsinki University Central Hospital, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caiyun Grace","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Wall Center for Pulmonary Vascular Disease, Cardiovascular Institute Stanford University, Stanford CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shailaja P.","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Wall Center for Pulmonary Vascular Disease, Cardiovascular Institute Stanford University, Stanford CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinicio","family":"de Jesus Perez","sequence":"additional","affiliation":[{"name":"Department of Medicine. Stanford University, Stanford CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Sawada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Wall Center for Pulmonary Vascular Disease, Cardiovascular Institute Stanford University, Stanford CA, USA"},{"name":"Department of Pediatrics, Mie University Graduate School of Medicine, Mie, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juha W.","family":"Koskenvuo","sequence":"additional","affiliation":[{"name":"Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland"},{"name":"Department of Clinical Physiology and Nuclear Medicine, HUS Medical Imaging Center, Helsinki University Central Hospital and University of Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Alvira","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Wall Center for Pulmonary Vascular Disease, Cardiovascular Institute Stanford University, Stanford CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marlene","family":"Rabinovitch","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Wall Center for Pulmonary Vascular Disease, Cardiovascular Institute Stanford University, Stanford CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tero-Pekka","family":"Alastalo","sequence":"additional","affiliation":[{"name":"Children's Hospital Helsinki, Pediatric Cardiology, University of Helsinki and Helsinki University Central Hospital, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2016,1,1]]},"reference":[{"key":"2021042614052455500_JCS169011C1","volume-title":"Angiogenesis","author":"Adair","year":"2010"},{"key":"2021042614052455500_JCS169011C2","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1038\/nrm2183","article-title":"Molecular regulation of angiogenesis and lymphangiogenesis","volume":"8","author":"Adams","year":"2007","journal-title":"Nat. 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