Why the study?
Peroxisome proliferator-activated receptor gamma activation reduces native aortic valve sclerosis progression, but its effect on bioprosthetic valve degeneration is unknown.
Does pioglitazone reduce the degeneration of biological aortic valve conduits in an implantation model in obese and hypercholesterolaemic rats?
Does pioglitazone reduce the degeneration of biological aortic valve conduits in an implantation model in obese and hypercholesterolaemic rats?
p-value: p=0.014 at 4 weeks, 0.045 at 12 weeks
In a rat model, systemic PPAR-gamma activation with pioglitazone decreased intima hyperplasia, calcification, and functional impairment of implanted cryopreserved allogenic aortic valve conduits.
OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Assmann et al. (2022) studied Obese and hypercholesterolaemic rats with implanted biological aortic valve conduits (n=40). Pioglitazone vs. Untreated rats was evaluated on Intima hyperplasia (p=0.014 at 4 weeks, 0.045 at 12 weeks).
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