Journal
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
Volume 51, Issue 5, Pages -Publisher
WILEY
DOI: 10.1111/eci.13470
Keywords
calcific aortic valve disease; calmodulin‐ dependent kinase II; osteogenesis; runt‐ related transcription factor 2; vascular endothelial growth factor
Funding
- Taipei Medical University [TMU109-AE1-B09]
- Wan Fang Hospital [104-wf-phd-02, 107-wf-eva-02, 107TMUWFH-01-1, 108TMU-WFH-01-3, 105-wfphd-01, 106-wf-eva-08]
- Ministry of Science and Technology, Taiwan [MOST106-2221-E030011-MY2, MOST106-2221-E030-012, MOST108-2314-B-038-120]
Ask authors/readers for more resources
This study found that VEGF can upregulate the expression of Runx2 in valvular interstitial cells through activating the IP3R/CaMKII/CREB signaling pathway, providing insights into its role in the pathogenesis of calcific aortic valve disease.
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 mu mol/L) and inositol triphosphate receptor inhibitor (2-aminoethyldiphenyl borate, 30 mu mol/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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available