Sun Lina, Chen Shuchun, Gao Haina, Ren Luping, Song Guangyao
Department of Endocrinology, The First Hospital of Qinhuangdao, Qinhuangdao, Hebei 06600, P.R. China.
Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China.
Int J Mol Med. 2017 Sep;40(3):637-646. doi: 10.3892/ijmm.2017.3048. Epub 2017 Jul 3.
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-κB (NF-κB) 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-κB 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-κB.
内皮祖细胞（EPCs）是预测心血管事件的一个独立因素。内脂素在各种代谢紊乱的发病机制中起重要作用。在本研究中，我们检测了内脂素对EPCs凋亡的影响及其潜在机制。用不同浓度的内脂素、FK866（内脂素抑制剂）和BAY11-7085 [简称为BAY11；核因子-κB（NF-κB）抑制剂]预处理培养的EPCs，以研究内脂素与EPCs凋亡之间的关系。用内脂素处理48小时后，EPCs凋亡呈剂量依赖性增加，Bax、半胱天冬酶-3和NF-κB在mRNA和蛋白水平的表达上调，而Bcl-2蛋白表达下降。与未处理的对照组相比，用150 ng/ml内脂素处理后，EPCs凋亡以及Bax和半胱天冬酶-3表达的增加显著，同时还诱导白细胞介素-6（IL-6）和细胞间黏附分子-1（ICAM-1）蛋白表达呈剂量依赖性显著增加。FK866预处理可抑制内脂素诱导的所有效应。EPCs先用BAY11预孵育1小时，然后用内脂素（150 ng/ml）处理48小时，也可消除内脂素诱导的凋亡；还消除了内脂素对半胱天冬酶-3､Bax､ICAM-1和IL-6表达的促进作用及其对Bcl-2蛋白表达的抑制作用。总体而言，我们的数据表明，内脂素部分通过调节NF-κB增加促炎介质的表达，从而诱导EPCs凋亡。
