Department of Cardiac Surgery and Research Group for Experimental Surgery, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
Research Group for Experimental Surgery, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
Eur J Cardiothorac Surg. 2022 Dec 2;63(1). doi: 10.1093/ejcts/ezad005.
Hypercholesterolaemia and obesity are risk factors for the development of calcified aortic valve disease and common comorbidities in respective patients. Peroxisome proliferator-activated receptor gamma activation has been shown to reduce the progression of native aortic valve sclerosis, while its effect on bioprosthetic valve degeneration is yet unknown. This project aims to analyse the impact of pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, on the degeneration of biological aortic valve conduits in an implantation model in obese and hypercholesterolaemic rats.
Cryopreserved allogenic rat aortic valve conduits (n = 40) were infrarenally implanted into Wistar rats on high-fat (34.6%) diet. One cohort was treated with pioglitazone (75 mg/kg chow; n = 20, group PIO) and compared to untreated rats (n = 20, group control). After 4 or 12 weeks, conduits were explanted and analysed by (immuno-)histology and real-time polymerase chain reaction.
A significantly decreased intima hyperplasia occurred in group PIO compared to control after 4 (P = 0.014) and 12 weeks (P = 0.045). Calcification of the intima was significantly decreased in PIO versus control at 12 weeks (P = 0.0001). No significant inter-group differences were shown for media calcification after 4 and 12 weeks. Echocardiographically, significantly lower regurgitation through the implanted aortic valve conduit was observed in PIO compared to control after 4 (P = 0.018) and 12 weeks (P = 0.0004). Inflammatory activity was comparable between both groups.
Systemic peroxisome proliferator-activated receptor gamma activation decreases intima hyperplasia and subsequent intima calcification of cryopreserved allografts in obese, hypercholesterolaemic recipients. Additionally, it seems to inhibit functional impairment of the implanted aortic valve. Further preclinical studies are required to determine the long-term impact of peroxisome proliferator-activated receptor gamma agonists on graft durability.
高胆固醇血症和肥胖是钙化性主动脉瓣疾病发展的危险因素，也是各自患者的常见合并症。过氧化物酶体增殖物激活受体γ的激活已被证明可减缓天然主动脉瓣硬化的进展，但其对生物瓣退行性变的影响尚不清楚。本项目旨在分析过氧化物酶体增殖物激活受体γ激动剂吡格列酮对肥胖和高胆固醇血症大鼠植入模型中生物主动脉瓣管道退行性变的影响。
将冷冻保存的同种异体大鼠主动脉瓣管道（n=40）在高脂（34.6%）饮食下植入 Wistar 大鼠肾下腹主动脉。一组用吡格列酮（75mg/kg 饲料；n=20，PIO 组）治疗，并与未治疗的大鼠（n=20，对照组）进行比较。4 或 12 周后，取出管道并通过（免疫）组织学和实时聚合酶链反应进行分析。
与对照组相比，PIO 组在 4 周（P=0.014）和 12 周（P=0.045）时内膜增生明显减少。在 12 周时，PIO 组的内膜钙化明显减少（P=0.0001）。在 4 周和 12 周时，两组之间的中膜钙化无显著差异。超声心动图显示，与对照组相比，在 4 周（P=0.018）和 12 周（P=0.0004）时，通过植入的主动脉瓣管道的反流明显减少。两组的炎症活性相当。
全身过氧化物酶体增殖物激活受体γ激活可减少肥胖、高胆固醇血症受者冷冻同种异体移植物的内膜增生和随后的内膜钙化。此外，它似乎抑制了植入的主动脉瓣功能障碍。需要进一步的临床前研究来确定过氧化物酶体增殖物激活受体γ激动剂对移植物耐久性的长期影响。
