• Shao-Jung Li, Yu-Hsun Kao, Cheng-Chih Chung, Wan-Li Cheng, Yung-Kuo Lin, and Yi-Jen Chen.
• Division of Cardiovascular Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
• Eur. J. Clin. Invest. 2021 May 1; 51 (5): e13470.

BackgroundCalcific aortic valve disease is associated with ageing and high mortality. However, no effective pharmacological treatment has been developed. Vascular endothelial growth factor (VEGF) and its receptor are overexpressed in the calcified aortic valve tissue. However, the role of VEGF in calcific aortic valve disease pathogenesis and its underlying mechanisms remain unclear.Materials And MethodsRunt-related transcription factor 2 expression and calcium-related signalling were investigated in porcine valvular interstitial cells with or without human VEGF-A recombinant protein (VEGF165 , 1-100 ng/mL) treatment and/or calmodulin-dependent kinase II (CaMKII) inhibitor (KN93, 10 µmol/L) and inositol triphosphate receptor inhibitor (2-aminoethyldiphenyl borate, 30 µmol/L) for 5 days.ResultsVEGF165 -treated cells had higher Runt-related transcription factor 2 expression and CaMKII/ adenosine 3',5'-monophosphate response element-binding protein (CREB) signalling activation than did control cells. KN93 reduced Runt-related transcription factor 2 expression and CREB phosphorylation in VEGF165 -treated cells. The 2-aminoethyldiphenyl borate also reduced Runt-related transcription factor 2 expression in VICs treated with VEGF165 .ConclusionVEGF upregulated Runt-related transcription factor 2 expression in VICs by activating the IP3R/CaMKII/CREB signalling pathway.© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

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