Visfatin induces the apoptosis of endothelial progenitor cells via the induction of pro-inflammatory mediators through the NF-κB pathway

Endothelial progenitor cells (EPCs) are an independent factor predicting cardiovascular events. Visfatin plays an important role in the pathogenesis of various metabolic disorders. In this study, we examined the effects of visfatin on the apoptosis of EPCs and the mechanisms underlying these effects. Cultured EPCs pre-treated with various concentrations of visfatin, FK866 (visfatin inhibitor) and BAY11-7085 [referred to as BAY11; nuclear factor-kappa B (NF-kappa B) inhibitor] were used to investigate the association between visfatin and EPC apoptosis. Following treatment with visfatin for 48 h, the EPCs exhibited a dose-dependent increase in apoptosis and an upregulated expression of Bax, caspase-3 and NF-kappa B at both the mRNA and protein level, and a decreased protein expression of Bcl-2. Compared with the untreated control group, the increase in EPC apoptosis, as well as in Bax and caspase-3 expression was significant following treatment with 150 ng/ml visfatin, which also induced a dose-dependent and significant increase in the protein expression of interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1). All the visfatin-induced effects were suppressed by pre-treatment with FK866. Pre-incubation of the EPCs with BAY11 for 1 h followed by treatment with visfatin (150 ng/ml) for 48 h also abolished visfatin-induced apoptosis; it also abolished the promoting effects of visfatin on the expression of caspase-3, Bax, ICAM-1 and IL-6, and its suppressive effects on the protein expression of Bcl-2. On the whole, our data indicate that visfatin induces EPC apoptosis by increasing the expression of pro-inflammatory mediators partly through the regulation of NF-kappa B.