Impaired progenitor cell activity in age-related endothelial dysfunction
Impaired progenitor cell activity in age-related endothelial dysfunction
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DOI：
10.1016/j.jacc.2004.12.074
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发表时间：
2005-05-03
影响因子：
24
通讯作者：
Kalka, C
中科院分区：
文献类型：
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作者：
Heiss, C;Keymel, S;Kalka, C
我们研究了人类年龄相关的内皮功能障碍是否伴随着内皮祖细胞（EPC）库的定量和定性改变。具有内皮表型的循环祖细胞有助于血管壁的再生和修复。内皮完整性丧失和FPC修饰之间的关联可能为研究这种年龄相关血管变化的机制性质提供背景。在20名无主要心血管危险因素的老年和年轻健康个体（分别为61 +/- 2岁和25 +/- 1岁）中，测定了内皮功能（通过超声确定肱动脉的血流介导的扩张）以及从外周血中分离的EPCs的数量和功能。老年受试者的肱动脉内皮依赖性舒张功能显著受损（血流介导的舒张[FAID] 5.2 +/- 0.5% vs. 7.1 +/- 0.6%; p < 0.05）。三硝酸甘油（GTN）后的内皮非依赖性扩张没有差异，但老年受试者的FMD/GTN比值显著较低（49 +/- 4% vs. 37 +/- 3%; p < 0.05），表明内皮功能障碍。循环EPCs（定义为外周血中CD 34/KDR或CD 133/KDR双阳性细胞）的数量无差异。相比之下，（39 +/- 6细胞S/mm（2）vs. 65 +/- 11细胞S/mm（2）; p < 0.05），迁移（80 +/-12 vs. 157 +/-16 cells/mm 2; p < 0.01）和增殖（0.20 +/-0.04 cpm vs.0.44 +/-0.07 cpm; p < 0.05）暗示来自老年受试者的EPC的功能损伤。FMD与EPC迁移（r = 0.52，p < 0.05）和EPC增殖（r = 0.49，p < 0.05）呈单因素相关。多变量分析表明，这两个功能特征是内皮功能的独立预测因子。内皮祖细胞对血管稳态的维持作用可能随着年龄的增长而减弱，这是基于功能缺陷，而不是CD 34/KDR或CD 133/KDR细胞的耗竭。(c)2005年，美国心脏病学会基金会。
We investigated whether human age-related endothelial dysfunction is accompanied by quantitative and qualitative alterations of the endothelial progenitor cell (EPC) pool. Circulating progenitor cells with an endothelial phenotype contribute to the regeneration and repair of the vessel wall. An association between the loss of endothelial integrity and FPC modification may provide a background to study the mechanistic nature of such age-related vascular changes. In 20 old and young healthy individuals (61 +/- 2 years and 25 +/- 1 year, respectively) without major cardiovascular risk factors, endothelial function, defined by flow-mediated dilation of the brachial artery via ultrasound, as well as the number and function of EPCs isolated from peripheral blood, were determined. Older subjects had significantly impaired endothelium-dependent dilation of brachial artery (flow-mediated dilation [FAID] 5.2 +/- 0.5% vs. 7.1 +/- 0.6%; p < 0.05). Endothelium-independent dilation after glycerol trinitrate (GTN) was not different, but the FMD/GTN ratio was significantly lower in old subjects (49 +/- 4% vs. 37 +/- 3%; p < 0.05), suggesting endothelial dysfunction. There were no differences in the numbers of circulating EPCs, defined as CD34/KDR or CD133/KDR double-positive cells in peripheral blood. In contrast, lower survival (39 +/- 6 ceHS/mm(2) vs. 65 +/- 11 cell S/mm(2); p < 0.05), migration (80 +/- 12 vs. 157 +/- 16 cells/mm 2; p < 0.01), and proliferation (0.20 +/- 0.04 cpm vs. 0.44 +/- 0.07 cpm; p < 0.05) implicate functional impairment of EPCs from old subjects. The FMD correlated univariately with EPC migration (r = 0.52, p < 0.05) and EPC proliferation (r = 0.49, p < 0.05). Multivariate analysis showed that both functional features represent independent predictors of endothelial function. Maintenance of vascular homeostasis by EPCs may be attenuated with age based on functional deficits rather than depletion of CD34/KDR or CD133/KDR cells. (c) 2005 by the American College of Cardiology Foundation.