{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:35:36Z","timestamp":1788273336191,"version":"build-2803163510"},"reference-count":85,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,11,6]],"date-time":"2022-11-06T00:00:00Z","timestamp":1667692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["R01-HL128628-01"],"award-info":[{"award-number":["R01-HL128628-01"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["T32HD087166"],"award-info":[{"award-number":["T32HD087166"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Obstetrics, Gynecology and Reproductive Biology at Michigan State University College of Human Medicine","award":["R01-HL128628-01"],"award-info":[{"award-number":["R01-HL128628-01"]}]},{"name":"Department of Obstetrics, Gynecology and Reproductive Biology at Michigan State University College of Human Medicine","award":["T32HD087166"],"award-info":[{"award-number":["T32HD087166"]}]},{"name":"March of Dimes Foundation Award","award":["R01-HL128628-01"],"award-info":[{"award-number":["R01-HL128628-01"]}]},{"name":"March of Dimes Foundation Award","award":["T32HD087166"],"award-info":[{"award-number":["T32HD087166"]}]},{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development Health","award":["R01-HL128628-01"],"award-info":[{"award-number":["R01-HL128628-01"]}]},{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development Health","award":["T32HD087166"],"award-info":[{"award-number":["T32HD087166"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Preeclampsia (PE) is one of the most common causes of maternal-fetal morbidity and mortality world-wide. While the underlying causes of PE remain elusive, aberrant trophoblast differentiation and function are thought to cause an imbalance of secreted angiogenic proteins resulting in systemic endothelial dysfunction and organ damage in the mother. The placental dysfunction is also characterized by a reduction of the transcription factor, peroxisome proliferator activated receptor \u03b3 (PPAR\u03b3) which normally promotes trophoblast differentiation and healthy placental function. This study aimed to understand how placental activation of PPAR\u03b3 effects the secretion of angiogenic proteins and subsequently endothelial function. To study this, healthy and PE placental tissues were cultured with or without the PPAR\u03b3 agonist, Rosiglitazone, and a Luminex assay was performed to measure secreted proteins from the placenta. To assess the angiogenic effects of placental activation of PPAR\u03b3, human umbilical vein endothelial cells (HUVECs) were cultured with the placental conditioned media and the net angiogenic potential of these cells was measured by a tube formation assay. This is the first study to show PPAR\u03b3\u2019s beneficial effect on the angiogenic profile in the human preeclamptic placenta through the reduction of anti-angiogenic angiopoietin-2 and soluble endoglin and the upregulation of pro-angiogenic placental growth factor, fibroblast growth factor-2, heparin-binding epidermal growth factor, and follistatin. The changes in the angiogenic profile were supported by the increased angiogenic potential observed in the HUVECs when cultured with conditioned media from rosiglitazone-treated preeclamptic placentas. The restoration of these disrupted pathways by activation of PPAR\u03b3 in the preeclamptic placenta offers potential to improve placental and endothelial function in PE.<\/jats:p>","DOI":"10.3390\/cells11213514","type":"journal-article","created":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T02:43:51Z","timestamp":1667789031000},"page":"3514","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The Potential for Placental Activation of PPAR\u03b3 to Improve the Angiogenic Profile in Preeclampsia"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0384-3348","authenticated-orcid":false,"given":"Brooke","family":"Grimaldi","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid-Reza","family":"Kohan-Ghadr","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Drewlo","sequence":"additional","affiliation":[{"name":"Biological Sciences Platform, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, Toronto M4N 3M5, Canada"},{"name":"Department of Obstetrics and Gynecology, Temerty Faculty of Medicine, University of Toronto, Toronto M5G 1E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S18","DOI":"10.1111\/nure.12055","article-title":"Epidemiology of preeclampsia: Impact of obesity","volume":"71","author":"Jeyabalan","year":"2013","journal-title":"Nutr. 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