Age-dependent depression in circulating endothelial progenitor cells in patients undergoing coronary artery bypass grafting.

Age-dependent depression in circulating endothelial progenitor cells in patients undergoing coronary artery bypass grafting.
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DOI:
10.1055/s-2004-816608
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发表时间:
2004-01
影响因子:
24
通讯作者:
R. Scheubel;H. Zorn;R. Silber;O. Kuss;H. Morawietz;J. Holtz;A. Simm
R. Scheubel;H. Zorn;R. Silber;O. Kuss;H. Morawietz;J. Holtz;A. Simm
中科院分区:
医学1区
文献类型:
--
作者:
R. Scheubel;H. Zorn;R. Silber;O. Kuss;H. Morawietz;J. Holtz;A. Simm

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目的探讨冠状动脉旁路移植术(CABG)患者年龄对循环内皮祖细胞(EPC)及其动员的影响。背景:内皮祖细胞能够促进组织缺血后修复性新生血管的形成。在实验模型中,修复性新生血管在衰老动物中受到损害,但内皮祖细胞在这种损害中的作用,特别是在人类中,尚不清楚。方法50例稳定性冠状动脉病变患者,年龄43~80岁,行冠状动脉旁路移植术,分别于术前、术中、术后6、12、24、72h测定外周血内皮祖细胞数、血浆白介素6、白介素8、白介素10、白介素18、血管内皮生长因子、胎盘生长因子水平。结果术前内皮祖细胞随着年龄的增加而降低,与血浆中血管内皮生长因子水平的降低相似。这些与年龄相关的下降不能用动脉粥样硬化危险因素或心功能的差异来解释。体外循环术后EPC、IL-6、IL-8、IL-10和血管内皮生长因子迅速动员,术后6h达到高峰。在整个观察期内,69岁患者的EPC和血管内皮生长因子水平持续降低,这不能用手术程序或炎性IL激活的差异来解释。结论尽管冠状动脉旁路移植术中内皮祖细胞显著增加,细胞趋化因子的释放也显著增加,但年龄仍是内皮祖细胞动员的主要限制因素。需要进一步的研究来改进老年患者内皮祖细胞的动员、体外扩增和重新移植的策略。
OBJECTIVES The effect of patient age on circulating endothelial progenitor cells (EPCs) and their mobilization during coronary artery bypass grafting (CABG) was assessed. BACKGROUND The EPCs are able to contribute to reparative neovascularization after tissue ischemia. In experimental models, reparative neovascularization is impaired in senescent animals, but the role of EPCs in this impairment, especially in humans, is unknown. METHODS In 50 consecutive patients (43 to 80 years old) with stable coronary artery disease undergoing CABG, the numbers of EPCs and the plasma levels of interleukin (IL)-6, IL-8, IL-10, and IL-18, as well as vascular endothelial growth factor (VEGF) and placental growth factor, were determined preoperatively, after coming off bypass, and 6, 12, 24, and 72 h postoperatively. RESULTS Preoperative values of EPCs were lowered with increasing age, similar to the lowering of plasma VEGF levels. These age-associated decreases could not be explained by differences in atherosclerotic risk factors or cardiac function. Bypass surgery induced a rapid mobilization in EPCs, IL-6, IL-8, IL-10, and VEGF, with a peak 6 h postoperatively. Persistently lower levels of EPCs and VEGF throughout the observation period were observed in patients >69 years old, which could not be explained by differences in the operative procedure or inflammatory IL activation. CONCLUSIONS Despite a significant increase in EPCs and release of cytochemokines during CABG, age is a major limiting factor for mobilization of EPCs. Further studies are necessary to improve the strategies for mobilization, ex vivo expansion, and re-transplantation of EPCs in aging patients.