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Vascular endothelial growth factor on Runt‐related transcript factor‐2 in aortic valve cells
Author(s) -
Li ShaoJung,
Kao YuHsun,
Chung ChengChih,
Cheng WanLi,
Lin YungKuo,
Chen YiJen
Publication year - 2021
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.13470
Subject(s) - creb , transcription factor , vascular endothelial growth factor , growth factor , kinase insert domain receptor , microbiology and biotechnology , biology , cancer research , vascular endothelial growth factor a , chemistry , medicine , endocrinology , receptor , biochemistry , gene , vegf receptors
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 calcium‐related signalling were investigated in porcine valvular interstitial cells with or without human VEGF‐A recombinant protein (VEGF 165 , 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 VEGF 165 ‐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 VEGF 165 ‐treated cells. The 2‐aminoethyldiphenyl borate also reduced Runt‐related transcription factor 2 expression in VICs treated with VEGF 165 . Conclusion VEGF upregulated Runt‐related transcription factor 2 expression in VICs by activating the IP3R/CaMKII/CREB signalling pathway.