Vascular Endothelial Growth Factor Promotes the Proliferative Capacity of Endothelial Progenitor Cells by Increasing Calcineurin Enzymatic Activity

Background Vascular endothelial growth factor(VEGF)has been shown to cross-talk with numerous signaling pathways on regulating the biological function of endothelial progenitor cells(EPC).Little is known about the role of VEGF on regulating the activation of calcineurin signal in EPC.Objective To investigate whether vascular endothelial growth factor(VEGF)regulates the proliferative capacity of endothelial progenitor cells(EPC)by the way of activating calcineurin(CaN)signal.Methods EPC were obtained from cultured mononuclear cells isolated from peripheral blood of healthy adults,and were received following approaches:Control,VEGF(50 μg/L),cyclosporin A(CsA,10 mg/L),and CsA+VEGF(incubation with CsA for 1 h before VEGF was added).CaN enzymatic activity and cell proliferation were assayed using colorimetric method.Cell apoptosis was determined by TUNEL staining.The expression of bcl2 and bax genes was investigated by RT-PCR analysis.Results Compared with the control group,VEGF(50 μg/L)significantly increased CaN enzymatic activity(+73%,P0.01),cell proliferation(+89%,P0.01),and bcl2 gene expression(+40%,P0.01).Pre-treated with cyclosporine(10 mg/L)markedly abrogated the aforementioned effects of VEGF.Compared with the VEGF group,CsA+VEGF decreased the CaN enzymatic activity,cell proliferation,and bcl2 gene expression 60%,78% and 82%,respectively,all P0.01)and increased the apoptotic rate of EPC.No statistic significant difference of bax gene expression was found between groups.Conclusion VEGF treatment promotes proliferative capacity of human EPC by activating CaN signal.