Bioprosthetic heart valve structural degeneration associated with metabolic syndrome: Mitigation with polyoxazoline modification.
Alexey AbramovYingfei XueAndrey ZakharchenkoMangesh KuradeRajesh Kumar SoniRobert J LevyGiovanni FerrariPublished in: Proceedings of the National Academy of Sciences of the United States of America (2022)
Bioprosthetic heart valves (BHV), made from glutaraldehyde-fixed xenografts, are widely used for surgical and transcatheter valve interventions but suffer from limited durability due to structural valve degeneration (SVD). We focused on metabolic syndrome (MetS), a risk factor for SVD and a highly prevalent phenotype in patients affected by valvular heart disease with a well-recognized cluster of comorbidities. Multicenter patient data (N = 251) revealed that patients with MetS were at significantly higher risk of accelerated SVD and required BHV replacement sooner. Using a next-generation proteomics approach, we identified significantly differential proteomes from leaflets of explanted BHV from MetS and non-MetS patients (N = 24). Given the significance of protein infiltration in MetS-induced SVD, we then demonstrated the protective effects of polyoxazoline modification of BHV leaflets to mitigate MetS-induced BHV biomaterial degeneration (calcification, tissue cross-linking, and microstructural changes) in an ex vivo serum model and an in vivo with MetS rat subcutaneous implants.
Keyphrases
- aortic valve
- mitral valve
- metabolic syndrome
- end stage renal disease
- ejection fraction
- chronic kidney disease
- aortic stenosis
- aortic valve replacement
- newly diagnosed
- heart failure
- transcatheter aortic valve replacement
- prognostic factors
- atrial fibrillation
- diabetic rats
- physical activity
- transcatheter aortic valve implantation
- insulin resistance
- climate change
- high glucose
- adipose tissue
- oxidative stress
- multiple sclerosis
- drug induced