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- Title
Vascular endothelial growth factor on Runt-related transcript factor-2 in aortic valve cells.
- Authors
Shao-Jung Li; Yu-Hsun Kao; Cheng-Chih Chung; Wan-Li Cheng; Yung-Kuo Lin; Yi-Jen Chen
- Abstract
Background: Calcific 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 methods: Runt-related transcription factor 2 expression and calciumrelated 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. Results: VEGF165-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. Conclusion: VEGF upregulated Runt-related transcription factor 2 expression in VICs by activating the IP3R/CaMKII/CREB signalling pathway.
- Subjects
VASCULAR endothelial growth factors; RUNX proteins; AORTIC valve; AORTIC valve diseases; RECOMBINANT proteins; PROTEIN kinases; ADENOSINES
- Publication
European Journal of Clinical Investigation, 2021, Vol 51, Issue 5, p1
- ISSN
0014-2972
- Publication type
Article
- DOI
10.1111/eci.13470