Diabetes-induced aortic valve degeneration in static cultivation and in a bioreactor system. Interactions between the cultivation environment and diabetes mellitus

Background: Type 2 diabetes mellitus is a prominent risk factor for the development and progression of calcific aortic valve disease; however, little is known about its molecular effect on aortic valve degeneration.Objective: In this study the influence of hyperinsulinemia and hyperglycemia, the two main characteristics of type 2 diabetes mellitus, on healthy aortic valve tissue was investigated. At the same time, the impact of biomechanical factors on diabetes-induced cell processes was taken into account.Material and methods: Ovine aortic valve tissue was cultivated for seven days under diabetic conditions, comparing a static cultivation environment with fixed aortic valves to a dynamic cultivation model with strain and shear stress. A computer-controlled bioreactor system was used that in addition to the pulsatile flow for valve opening also regulated other physiological parameters.Results: Dynamic cultivation resulted in significantly stronger fibrosis in aortic valve tissue compared to static cultivation, while hyperinsulinemia and hyperglycemia had no impact on the fibrotic processes; however, the expression of differentiation markers and matrix proteins was altered in an environment-dependent manner by diabetic treatment. In addition, chronic hyperinsulinemia and hyperglycemia modulated the insulin signalling pathways that affect the insulin response of the tissue.Conclusion: These data demonstrate a complex interplay of diabetic conditions and biomechanical factors that influence the remodelling and degeneration of aortic valve tissue.