ArticleInternational journal of molecular sciences2021
Crosstalk of Diabetic Conditions with Static Versus Dynamic Flow Environment-Impact on Aortic Valve Remodeling.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- Shared pathophysiological mechanisms between diabetes and calcific aortic valve disease: an immunometabolic perspective.Cardiovascular diabetology · 2026Review
- Metformin mitigates aortic valve degeneration in an ex vivo three-dimensional tissue model.Scientific reports · 2025Article
- Functional Role of miR-138-5p and miR-200b-3p in Testicular Germ Cell Tumors: Molecular Insights into Seminoma and Teratoma Pathogenesis.International journal of molecular sciences · 2025Article
- Diabetes and calcific aortic valve disease: implications of glucose-lowering medication as potential therapy.Frontiers in pharmacology · 2025Review
- Diabetes and calcific aortic valve disease: controversy of clinical outcomes in diabetes after aortic valve replacement.Frontiers in endocrinology · 2025Review
- Interactive contribution of hyperinsulinemia, hyperglycemia, and mammalian target of rapamycin signaling to valvular interstitial cell differentiation and matrix remodeling.Frontiers in cardiovascular medicine · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Type 2 diabetes mellitus (T2D) is one of the prominent risk factors for the development and progression of calcific aortic valve disease. Nevertheless, little is known about molecular mechanisms of how T2D affects aortic valve (AV) remodeling. In this study, the influence of hyperinsulinemia and hyperglycemia on degenerative processes in valvular tissue is analyzed in intact AV exposed to an either static or dynamic 3D environment, respectively. The complex native dynamic environment of AV is simulated using a software-governed bioreactor system with controlled pulsatile flow. Dynamic cultivation resulted in significantly stronger fibrosis in AV tissue compared to static cultivation, while hyperinsulinemia and hyperglycemia had no impact on fibrosis. The expression of key differentiation markers and proteoglycans were altered by diabetic conditions in an environment-dependent manner. Furthermore, hyperinsulinemia and hyperglycemia affect insulin-signaling pathways. Western blot analysis showed increased phosphorylation level of protein kinase B (AKT) after acute insulin stimulation, which was lost in AV under hyperinsulinemia, indicating acquired insulin resistance of the AV tissue in response to elevated insulin levels. These data underline a complex interplay of diabetic conditions on one hand and biomechanical 3D environment on the other hand that possesses an impact on AV tissue remodeling.
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Registered trials
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