Aortic valve replacement for severe stenosis is a standard procedure in cardiovascular medicine. However, the use of biological prostheses has limitations especially in young patients due to calcifying degeneration resulting in implant failure. Pioglitazone, a PPAR-gamma agonist, was shown to decrease the degeneration of native aortic valves. In this study, we aim to examine the impact of pioglitazone on inflammation and calcification of aortic valve conduits in a rat model.Cryopreserved aortic valve conduits (AoC) (n=40) were infrarenally implanted into Wistar rats treated with pioglitazone (75mg/kg chow; n=20, PIO) or untreated (n=20, controls). After 4 or 12 weeks, AoC were explanted and analyzed by histology, immunohistology and PCR.Pioglitazone significantly decreased the expression of inflammatory markers and reduced the macrophage-mediated inflammation in PIO compared to controls after 4 (p=0.03) and 12 weeks (p=0.012). Chondrogenic transformation was significantly decreased in PIO after 12 weeks (p=0.001). Calcification of the intima and media was significantly reduced after 12 weeks in PIO versus controls (intima: p=0.008; media: p=0.025). Moreover, echocardiography revealed significantly better functional outcome of the AoC in PIO after 12 weeks compared to control. Interestingly, significantly increased intima hyperplasia could be observed in PIO compared to controls after 12 weeks (p=0.017).Systemic PPAR-gamma activation prevents inflammation as well as intima and media calcification in aortic valve conduits, and seems to inhibit functional impairment of the implanted aortic valve. To further elucidate the therapeutic role of PPAR-gamma regulation for graft durability, translational studies and long-term follow-up data should be striven for.

中文翻译：

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过氧化物酶体增殖物激活受体γ (PPAR-γ) 激动剂在抵抗心血管移植物退化中的作用。


主动脉瓣置换术治疗严重狭窄是心血管医学的标准手术。然而，生物假体的使用存在局限性，尤其是在年轻患者中，因为钙化变性会导致植入失败。吡格列酮是一种 PPAR-γ 激动剂，已被证明可以减少天然主动脉瓣的退化。在本研究中，我们旨在研究吡格列酮对大鼠模型主动脉瓣导管炎症和钙化的影响。将冷冻保存的主动脉瓣导管（AoC）（n = 40）植入经吡格列酮（75mg/kg）治疗的Wistar大鼠肾下。食物；n=20，PIO）或未经处理（n=20，对照）。 4 周或 12 周后，AoC 被外植，并通过组织学、免疫组织学和 PCR 进行分析。与对照组相比，4 周（p=0.03）和 12 周（p =0.012）。 12 周后，PIO 中的软骨转化显着减少 (p=0.001)。 12 周后，PIO 与对照组相比，内膜和中膜的钙化显着减少（内膜：p=0.008；中膜：p=0.025）。此外，超声心动图显示 12 周后 PIO 中 AoC 的功能结果明显优于对照组。有趣的是，12 周后，与对照组相比，PIO 中可观察到内膜增生显着增加 (p=0.017)。全身性 PPAR-gamma 激活可预防主动脉瓣导管的炎症以及内膜和中膜钙化，并且似乎可以抑制主动脉瓣导管的功能损伤。植入主动脉瓣。为了进一步阐明 PPAR-gamma 调节对移植物耐久性的治疗作用，应争取转化研究和长期随访数据。