The impact of the capability of circulating progenitor cell to differentiate on myocardial salvage in patients with primary acute myocardial infarction
The impact of the capability of circulating progenitor cell to differentiate on myocardial salvage in patients with primary acute myocardial infarction
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DOI：
10.1161/circulationaha.105.000588
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发表时间：
2006-07-04
期刊：
影响因子：
37.8
通讯作者：
Murohara, Toyoaki
中科院分区：
文献类型：
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作者：
Numaguchi, Yasushi;Sone, Takahito;Murohara, Toyoaki
背景-循环内皮祖细胞（EPCs）参与血管生成，并在急性心肌梗死（AMI）后动员。为了检验EPCs的血管生成功能影响心肌梗死后（MI）心肌挽救的假设，我们评估了EPCs的数量和潜在分化，并将这些数据与MI后6个月的临床参数进行了比较。方法和结果：入选了51例原发性AMI患者（年龄61 ± 8岁，平均值± SD），这些患者成功接受了支架植入术治疗。通过流式细胞术定量鉴定为CD 45（低）、CD 34（+）、CD 133（+）和VEGFR 2（+）的EPC。EPCs分化为内皮细胞（EPC分化）的潜力也通过培养7天后CD 31和VEGFR 2的上调来证实。根据EPC分数的比例，将患者分为2组（临界值=中位数）。虽然分化组（n=26）和未分化组（n=25）的平均峰值CK漏出率和平均危险面积显示的心肌损害无差异，但分化组的贴壁细胞数高于未分化组（P=0.023）。急性期采用I-123-BMIPP心肌显像，慢性期采用Tc-99 m-tetrofosmin心肌显像评价左室功能和心肌缺血损伤面积。我们发现心肌挽救率的增加（P=0.0091），收缩末期容积减少（P=0.012），射血分数恢复（P=0.011）发生在分化EPCs组比未分化组。结论-在原发性AMI患者中，EPCs的分化能力影响功能改善和梗死面积缩小，这表明操纵EPCs可能是挽救缺血性损伤的新的治疗靶点。
Background-Circulating endothelial progenitor cells (EPCs) are known to be involved in vasculogenesis and mobilized after acute myocardial infarction (AMI). To test the hypothesis that the angiogenic function of EPCs affects post-myocardial infarction (MI) myocardial salvage, we evaluated the number and potential differentiation of EPCs and compared these data with clinical parameters 6 months after MI.Methods and Results-Consecutive 51 patients (age, 61 +/- 8 years, mean +/- SD) with primary AMI who were successfully treated with stenting were enrolled. EPC identified as CD45(low), CD34(+), CD133(+), and VEGFR2(+) was quantified by a flow cytometry. The potential of EPCs to differentiate into endothelial cells (EPC differentiation) was also confirmed by the upregulation of CD31 and VEGFR2 after 7 days of culture. According to the proportion of EPC fraction, patients were divided into 2 groups (cut-off value=median). Although no difference was seen in myocardial damage shown by mean peak CK leakage and mean area at risk between the differentiated group (n=26) and nondifferentiated group (n=25), the number of attached cell was greater in differentiated group than in the nondifferentiated group (P=0.023). Left ventricular function and ischemic damaged area were assessed by scintigraphic images of I-123-BMIPP in the acute phase and Tc-99m-tetrofosmin in the chronic phase. We found that a greater increase in myocardial salvage (P=0.0091), decrease in end-systolic volume (P=0.012), and recovery of ejection fraction (P=0.011) occurred in the group with differentiated EPCs than in the nondifferentiated group.Conclusions-In patients with primary AMI, the capability of EPCs to differentiate influences the functional improvement and infarct size reduction, indicating that manipulation of EPCs could be a novel therapeutic target to salvage ischemic damage.