Hill Jonathan M, Zalos Gloria, Halcox Julian P J, Schenke William H, Waclawiw Myron A, Quyyumi Arshed A, Finkel Toren
Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1622, USA.
N Engl J Med. 2003 Feb 13;348(7):593-600. doi: 10.1056/NEJMoa022287.
Cardiovascular risk factors contribute to atherogenesis by inducing endothelial-cell injury and dysfunction. We hypothesized that endothelial progenitor cells derived from bone marrow have a role in ongoing endothelial repair and that impaired mobilization or depletion of these cells contributes to endothelial dysfunction and cardiovascular disease progression.
We measured the number of colony-forming units of endothelial progenitor cells in peripheral-blood samples from 45 men (mean [+/-SE] age, 50+/-2 years). The subjects had various degrees of cardiovascular risk but no history of cardiovascular disease. Endothelium-dependent and endothelium-independent function was assessed by high-resolution ultrasonography of the brachial artery.
We observed a strong correlation between the number of circulating endothelial progenitor cells and the subjects' combined Framingham risk factor score (r=-0.47, P=0.001). Measurement of flow-mediated brachial-artery reactivity also revealed a significant relation between endothelial function and the number of progenitor cells (r=0.59, P<0.001). Indeed, the levels of circulating endothelial progenitor cells were a better predictor of vascular reactivity than was the presence or absence of conventional risk factors. In addition, endothelial progenitor cells from subjects at high risk for cardiovascular events had higher rates of in vitro senescence than cells from subjects at low risk.
In healthy men, levels of endothelial progenitor cells may be a surrogate biologic marker for vascular function and cumulative cardiovascular risk. These findings suggest that endothelial injury in the absence of sufficient circulating progenitor cells may affect the progression of cardiovascular disease.
心血管危险因素通过诱导内皮细胞损伤和功能障碍促进动脉粥样硬化形成。我们推测，源自骨髓的内皮祖细胞在持续的内皮修复中发挥作用，这些细胞的动员受损或耗竭会导致内皮功能障碍和心血管疾病进展。
我们测量了45名男性（平均[±标准误]年龄，50±2岁）外周血样本中内皮祖细胞的集落形成单位数量。这些受试者有不同程度的心血管风险，但无心血管疾病史。通过肱动脉高分辨率超声评估内皮依赖性和非内皮依赖性功能。
我们观察到循环内皮祖细胞数量与受试者的弗雷明汉综合危险因素评分之间存在强相关性（r = -0.47，P = 0.001）。对血流介导的肱动脉反应性的测量还揭示了内皮功能与祖细胞数量之间的显著关系（r = 0.59，P < 0.001）。实际上，循环内皮祖细胞水平比传统危险因素的有无更能预测血管反应性。此外，心血管事件高风险受试者的内皮祖细胞在体外的衰老率高于低风险受试者的细胞。
在健康男性中，内皮祖细胞水平可能是血管功能和累积心血管风险的替代生物学标志物。这些发现表明，在缺乏足够循环祖细胞的情况下，内皮损伤可能会影响心血管疾病的进展。
