In a diabetic rat model, pioglitazone significantly reduced bioprosthetic graft media thickness at 12 weeks (p=0.0107) and inhibited graft media calcification (p=0.0079).
Does pioglitazone prevent calcific bioprosthetic degeneration of aortic grafts in a diabetic rat model?
In a diabetic rat model, PPAR-gamma activation with pioglitazone inhibits bioprosthetic aortic graft degeneration and calcification.
p-value: p=0.0079
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.
Katahira et al. (2021) studied Diabetes mellitus with bioprosthetic-valve-bearing aortic grafts. Pioglitazone vs. Normal chow without STZ / Diabetic controls was evaluated on Calcific bioprosthetic degeneration (media thickness and calcification) (p=0.0079). In a diabetic rat model, pioglitazone significantly reduced bioprosthetic graft media thickness at 12 weeks (p=0.0107) and inhibited graft media calcification (p=0.0079).