Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, Zeiher A M, Dimmeler S
Division of Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Germany.
Circ Res. 2001 Jul 6;89(1):E1-7. doi: 10.1161/hh1301.093953.
Recent studies provide increasing evidence that postnatal neovascularization involves bone marrow-derived circulating endothelial progenitor cells (EPCs). The regulation of EPCs in patients with coronary artery disease (CAD) is unclear at present. Therefore, we determined the number and functional activity of EPCs in 45 patients with CAD and 15 healthy volunteers. The numbers of isolated EPCs and circulating CD34/kinase insert domain receptor (KDR)-positive precursor cells were significantly reduced in patients with CAD by approximately 40% and 48%, respectively. To determine the influence of atherosclerotic risk factors, a risk factor score including age, sex, hypertension, diabetes, smoking, positive family history of CAD, and LDL cholesterol levels was used. The number of risk factors was significantly correlated with a reduction of EPC levels (R=-0.394, P=0.002) and CD34-/KDR-positive cells (R=-0.537, P<0.001). Analysis of the individual risk factors demonstrated that smokers had significantly reduced levels of EPCs (P<0.001) and CD34-/KDR-positive cells (P=0.003). Moreover, a positive family history of CAD was associated with reduced CD34-/KDR-positive cells (P=0.011). Most importantly, EPCs isolated from patients with CAD also revealed an impaired migratory response, which was inversely correlated with the number of risk factors (R=-0.484, P=0.002). By multivariate analysis, hypertension was identified as a major independent predictor for impaired EPC migration (P=0.043). The present study demonstrates that patients with CAD revealed reduced levels and functional impairment of EPCs, which correlated with risk factors for CAD. Given the important role of EPCs for neovascularization of ischemic tissue, the decrease of EPC numbers and activity may contribute to impaired vascularization in patients with CAD. The full text of this article is available at http://www.circresaha.org.
近期研究提供了越来越多的证据表明，出生后新血管形成涉及骨髓来源的循环内皮祖细胞（EPCs）。目前，冠状动脉疾病（CAD）患者中EPCs的调控尚不清楚。因此，我们测定了45例CAD患者和15名健康志愿者体内EPCs的数量和功能活性。CAD患者中分离出的EPCs数量以及循环CD34/激酶插入结构域受体（KDR）阳性前体细胞数量分别显著减少了约40%和48%。为了确定动脉粥样硬化危险因素的影响，我们使用了一个包括年龄、性别、高血压、糖尿病、吸烟、CAD家族史阳性以及低密度脂蛋白胆固醇水平的危险因素评分。危险因素数量与EPC水平降低（R=-0.394，P=0.002）以及CD34-/KDR阳性细胞数量减少（R=-0.537，P<0.001）显著相关。对个体危险因素的分析表明，吸烟者的EPCs水平（P<0.001）和CD34-/KDR阳性细胞数量（P=0.003）显著降低。此外，CAD家族史阳性与CD34-/KDR阳性细胞数量减少相关（P=0.011）。最重要的是，从CAD患者中分离出的EPCs还显示出迁移反应受损，这与危险因素数量呈负相关（R=-0.484，P=0.002）。通过多变量分析，高血压被确定为EPC迁移受损的主要独立预测因素（P=0.043）。本研究表明，CAD患者的EPCs水平降低且功能受损，这与CAD的危险因素相关。鉴于EPCs对缺血组织新血管形成的重要作用，EPC数量和活性的降低可能导致CAD患者血管生成受损。本文全文可在http://www.circresaha.org获取。
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