Combination of exendin-4 and DPP-4 silencing promoted angiogenesis of human coronary artery endothelial cells via activation of PI3K/Akt pathway.

ABSTRACT

This study was aimed to explore the combined effects of Exendin-4 with dipeptidyl peptidase-IV (DPP-4) silencing on vascular endothelial growth factor (VEGF)-induced cell proliferation and angiogenesis in Human Coronary Artery Endothelial Cells (HCAECs), as well as the underlying molecular mechanisms which were involved in this process. HCAECs were treated by exendin-4, small interfering RNA (siRNA) targeting DPP-4 (DPP-4-siRNA) or exendin-4 plus DPP-4-siRNA, respectively. Cell migration, proliferation and angiogenesis in vitro were assessed by scratch-wound assay, MTT, tran swell assay, and matrigel tube formation, respectively. Cell apoptosis was investigated by TUNEL assay. Expression of apoptosis and PI3K/Akt related proteins were assessed by Western blotting. Incubation of HCAECs with exendin-4 and silencing of DPP-4 both caused an increase in cell proliferation, migration and tube formation, while a significant decrease in apoptosis (all p<0.05). Furthermore, the combination of the exendin-4 and silencing of DPP-4 had additional effects on HCAECs. Protein levels of p-Akt and p-PI3K were markedly increased by exendin-4 incubation, silencing of DPP-4 in HCAECs. These results suggest that combination of exendin-4 and silencing of DPP-4 had additional promoted effects on angiogenesis of HCAECs via activation of PI3K/Akt pathway. Our study indicated an alternative therapeutic strategy for atherosclerotic neovascularization.