血管内皮生长因子激活钙调神经磷酸酶促进内皮祖细胞增殖  

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

作　　者：杨龙[1] 杨新春[2] 杨军珂[3] 

机构地区：[1]贵州省遵义医院心内科,贵州遵义563002 [2]首都医科大学附属北京朝阳医院心脏中心,北京100000 [3]中国人民解放军第二炮兵总医院心内科,北京100000

出　　处：《中华高血压杂志》2009年第3期246-250,共5页Chinese Journal of Hypertension

摘　　要：背景血管内皮生长因子(VEGF)在内皮祖细胞(EPC)生物活性的调控中涉及多条信号通路,但是否通过调控钙调神经磷酸酶(CaN)信号通路而影响EPC活性尚不清楚。目的探讨钙调神经磷酸酶(CaN)在血管内皮生长因子(VEGF)调节EPC增殖活性中的作用。方法采用密度梯度离心法分离外周血单个核细胞,贴壁培养获得EPC,分四组:对照组;VEGF组(VEGF50μg/L干预时间48h);环孢素A组(CsA10mg/L干预48h);环孢素A+VEGF组(CsA10mg/L干预1h,再予VEGF50μg/L干预时间48h)。比色法测定CaN活性及EPC增殖能力;TUNEL染色检测EPC凋亡;逆转录聚合酶链法检测bcl2和bax基因表达。结果VEGF刺激明显增强CaN活性(与对照组比较增加73%,P<0.01),促进EPC增殖(与对照组比较增加89%,P<0.01),增强bcl2基因表达(与对照组比较增加40%,P<0.05)。CsA预处理明显抑制VEGF的上述作用[CsA+VEGF组与VEGF组比较,CaN活性减弱60%(P<0.01),增殖能力减弱78%(P<0.01),bcl2基因表达减弱82%(P<0.01)],并增加细胞凋亡(凋亡率:CsA组:23.7%比对照组:3.3%,P<0.01)。VEGF和CsA干预对bax基因表达无明显影响。结论VEGF可通过激活CaN而促进EPC增殖活性。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%, P〈0.01）, cell proliferation （＋89%, P〈0.01）, and bcl2 gene expression （＋40%, P〈0.01）. Pretreated with eyelosporine （10 mg/LI 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 P〈0.01） and increased the apoptotie rate of EPC. No statistic significant differenee of bax gene expression was found between groups. Conclusion VEGF treatment promotes proliferative capacity of human EPC by activating CaN signal.

关 键 词：内皮祖细胞 血管内皮生长因子 钙调神经磷酸酶 

分 类 号：R543[医药卫生—心血管疾病]