Keymel Stefanie, Kalka Christoph, Rassaf Tienush, Yeghiazarians Yerem, Kelm Malte, Heiss Christian
Medical Clinic I, Dept. of Medicine, Division of Cardiology, Pulmonology, and Vascular Medicine, RWTH University Hospital Aachen, Pauwelstrasse 30, 52074, Aachen, Germany.
Basic Res Cardiol. 2008 Nov;103(6):582-6. doi: 10.1007/s00395-008-0742-z. Epub 2008 Aug 14.
We investigated whether qualitative or quantitative alterations of the endothelial progenitor cell (EPC) pool predict age-related structural vessel wall changes.
We have previously shown that age-related endothelial dysfunction is accompanied by qualitative rather than quantitative changes of EPCs. Animal studies suggest that impaired EPC functions lead to accelerated arterial intimal thickening.
Intima-media thickness (IMT) was measured in the common carotid artery in our previously published groups of younger (25 +/- 1 years, n = 20) and older (61 +/- 2 years, n = 20) healthy non-smoking volunteers without arterial hypertension, hypercholesterolemia, and diabetes mellitus. Endothelial progenitor cells (EPCs, KDR(+)/CD34(+) and KDR(+)/CD133(+)) were counted in peripheral blood using flow cytometry. In ex vivo expanded EPCs, the function was determined as chemotaxis to VEGF, proliferation, and survival.
We observed thicker IMT in older as compared to younger subjects (0.68 +/- 0.03 mm Vs. 0.48 +/- 0.02 mm, P < 0.001). Importantly, there were significant inverse univariate correlations between IMT, EPC chemotaxis, and survival (r = -0.466 P < 0.05; r = -0.463, P < 0.01). No correlation was observed with numbers of circulating EPCs. Multivariate regression analysis revealed that age, mean arterial pressure and migration of EPCs were independent predictors of IMT (R (2 )= 0.58).
Impaired EPC function may lead to accelerated vascular remodeling due to chronic impairment of endothelial maintenance.
我们研究了内皮祖细胞（EPC）池的定性或定量改变是否能预测与年龄相关的血管壁结构变化。
我们之前已经表明，与年龄相关的内皮功能障碍伴随着EPC的定性而非定量变化。动物研究表明，EPC功能受损会导致动脉内膜增厚加速。
在我们之前发表的年轻（25±1岁，n = 20）和年长（61±2岁，n = 20）健康非吸烟志愿者组中，测量颈总动脉的内膜中层厚度（IMT），这些志愿者无动脉高血压、高胆固醇血症和糖尿病。使用流式细胞术对外周血中的内皮祖细胞（EPC，KDR(+)/CD34(+)和KDR(+)/CD133(+)）进行计数。在体外扩增的EPC中，将功能确定为对VEGF的趋化性、增殖和存活。
我们观察到，与年轻受试者相比，年长受试者的IMT更厚（0.68±0.03mm对0.48±0.02mm，P < 0.001）。重要的是，IMT、EPC趋化性和存活之间存在显著的负单变量相关性（r = -0.466，P < 0.05；r = -0.463，P < 0.01）。未观察到与循环EPC数量的相关性。多变量回归分析显示，年龄、平均动脉压和EPC的迁移是IMT的独立预测因素（R (2)= 0.58）。
EPC功能受损可能由于内皮维持的慢性损害而导致血管重塑加速。
