Differential functions of genes regulated by VEGF–NFATc1 signaling pathway in the migration of pulmonary valve endothelial cells

We have reported that vascular endothelial growth factor (VEGF)‐A induces the proliferation of human pulmonary valve endothelial cells (HPVECs) through nuclear factor in activated T cells (NFAT)c1 activation [1]. Here we show that VEGF‐A increases the migration of HPVECs through NFATc1 activation, suggesting that VEGF‐A/NFATc1 regulates the migration of HPVECs. To learn how this pathway may be involved in post‐natal valvular repair, HPVECs were treated with VEGF‐A, with or without cyclosporine A to selectively block VEGF–NFATc1 signaling. Down Syndrome critical region 1 (DSCR1) and heparin‐binding EGF‐like growth factor (HB‐EGF) are two genes identified by DNA microarray as being up‐regulated by VEGF‐A in a cyclosporine‐A‐sensitive manner. DSCR1 silencing increased the migration of ovine valve endothelial cells, whereas HB‐EGF silencing inhibited migration. This differential effect suggests that VEGF‐A/NFATc1 signaling might be a crucial coordinator of endothelial cell migration in post‐natal valves.