Ppar-gamma activation may inhibit the in vivo degeneration of bioprosthetic aortic and aortic valve grafts under diabetic conditions

Shintaro Katahira, Yukiharu Sugimura, Sophia Grupp, Robin Doepp, Jessica Isabel Selig, Mareike Barth, Artur Lichtenberg, Payam Akhyari

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number11081
JournalInternational journal of molecular sciences
Volume22
Issue number20
DOIs
Publication statusPublished - 2021 Oct 1
Externally publishedYes

Keywords

  • Allograft
  • Bioprosthetic valve
  • Degeneration
  • Diabetes mellitus
  • Pioglitazone
  • PPAR-gamma

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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