Crosstalk of Diabetic Conditions with Static Versus Dynamic Flow Environment—Impact on Aortic Valve Remodeling

International Journal of Molecular Sciences

Payam Akhyari¹  Jessica I. Selig¹  Naima Niazy¹  Artur Lichtenberg¹  Joana Boulgaropoulos¹  Mareike Barth¹  Ralf Westenfeld²  Patrick Horn²  Karlheinz Preuß³  D. Margriet Ouwens⁴ 

[1] Department of Cardiac Surgery, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany;Department of Cardiology, Pneumology and Angiology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Moorenstraße 5, 40225 Düsseldorf, Germany;Faculty of Biotechnology, Bioprocessing, Modulation and Simulation, University of Applied Sciences Mannheim, Paul-Wittsack-Straße 10, 68163 Mannheim, Germany;Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center (DDZ), Auf’m Hennekamp 65, 40225 Düsseldorf, Germany;

关键词: aortic valve stenosis;    calcific aortic valve disease;    fibrosis;    diabetes mellitus;    hyperinsulinemia;    hyperglycemia;   

DOI  :  10.3390/ijms22136976

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown