{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T10:16:09Z","timestamp":1784715369006,"version":"3.55.0"},"reference-count":23,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: We aimed to examine the anti-calcification and anti-inflammatory effects of pioglitazone as a PPAR-gamma agonist on bioprosthetic-valve-bearing aortic grafts in a rat model of diabetes mellitus (DM). Methods: DM was induced in male Wistar rats by high-fat diet with an intraperitoneal streptozotocin (STZ) injection. The experimental group received additional pioglitazone, and controls received normal chow without STZ (n = 20 each group). Cryopreserved aortic donor grafts including the aortic valve were analyzed after 4 weeks and 12 weeks in vivo for analysis of calcific bioprosthetic degeneration. Results: DM led to a significant media proliferation at 4 weeks. The additional administration of pioglitazone significantly increased circulating adiponectin levels and significantly reduced media thickness at 4 and 12 weeks, respectively (p = 0.0002 and p = 0.0107, respectively). Graft media calcification was highly significantly inhibited by pioglitazone after 12 weeks (p = 0.0079). Gene-expression analysis revealed a significant reduction in relevant chondro-osteogenic markers osteopontin and RUNX-2 by pioglitazone at 4 weeks. Conclusions: Under diabetic conditions, pioglitazone leads to elevated circulating levels of adiponectin and to an inhibition of bioprosthetic graft degeneration, including lower expression of chondro-osteogenic genes, decreased media proliferation, and inhibited graft calcification in a small-animal model of DM.<\/jats:p>","DOI":"10.3390\/ijms222011081","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T22:42:18Z","timestamp":1634251338000},"page":"11081","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["PPAR-Gamma Activation May Inhibit the In Vivo Degeneration of Bioprosthetic Aortic and Aortic Valve Grafts under Diabetic Conditions"],"prefix":"10.3390","volume":"22","author":[{"given":"Shintaro","family":"Katahira","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich-Heine-University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0217-7363","authenticated-orcid":false,"given":"Yukiharu","family":"Sugimura","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich-Heine-University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Grupp","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich-Heine-University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Doepp","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich-Heine-University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica Isabel","family":"Selig","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich-Heine-University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mareike","family":"Barth","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich-Heine-University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur","family":"Lichtenberg","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich-Heine-University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6452-8678","authenticated-orcid":false,"given":"Payam","family":"Akhyari","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich-Heine-University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1161\/ATVBAHA.114.304205","article-title":"Early Development of Calcific Aortic Valve Disease and Left Ventricular Hypertrophy in a Mouse Model of Combined Dyslipidemia and Type 2 Diabetes Mellitus","volume":"34","author":"Bouchareb","year":"2014","journal-title":"Arter. 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