Department of Cardiovascular Diseases, San Filippo Neri Hospital, Rome, Italy.
JACC Cardiovasc Interv. 2010 Jan;3(1):78-86. doi: 10.1016/j.jcin.2009.10.020.
We prospectively investigated the relationship of circulating endothelial progenitor cells at time of percutaneous coronary intervention to the subsequent development of in-stent restenosis or progression of coronary atherosclerosis.
Endothelial progenitor cells provide an endogenous repair mechanism of the dysfunctional endothelium and therefore can play a pathogenic role in coronary atherosclerosis.
We studied 155 consecutive stable angina patients (92 men, age 60 +/- 11 years). All patients had flow cytometry the day before elective percutaneous coronary intervention in order to derive subpopulations of endothelial progenitor cells. A control group of 20 normal subjects was considered for comparison.
At 8-month control angiography, 30 patients showed in-stent restenosis (restenosis group), 22 patients showed progression of coronary atherosclerosis (progression group), whereas the remaining 103 patients had neither in-stent restenosis nor progression of coronary atherosclerosis (stable group). Comparison of the 3 groups did not show any difference in risk factors, cardiac morphology and function, extension of coronary artery disease, and treatment. Absolute numbers of CD34+/KDR+/CD45- cells (i.e., progenitors of endothelial lineage) measured in the restenosis group (1.41 +/- 0.64 cells/microl) were significantly higher than in the progression, stable, and control groups (1.03 +/- 0.53 cells/microl, 1.07 +/- 0.46 cells/microl, and 0.95 +/- 0.44 cells/microl, respectively, p < 0.05). Similarly, CD133+/KDR+/CD45- cells (i.e., progenitors of endothelial cells at an earlier stage) were significantly higher in the restenosis (0.63 +/- 0.23 cells/microl) compared with progression, stable, and control groups (0.33 +/- 0.19 cells/microl, 0.41 +/- 0.32 cells/microl, and 0.36 +/- 0.15 cells/microl, respectively, p < 0.001). Also, numbers of CD14+/CD45+ cells (i.e., which have a role in angiogenesis via a paracrine effect) were significantly different among the restenosis, progression, stable, and control groups (0.72 +/- 0.56 cells/microl vs. 0.51 +/- 0.52 cells/microl vs. 0.28 +/- 0.54 cells/microl vs. 0.62 +/- 0.67 cells/microl, respectively, p < 0.05), whereas CD105+/CD45-/CD34- cells (i.e., which have a receptor for transforming growth factor-beta) were similar among groups.
Patients with restenosis have higher numbers of subpopulations of endothelial progenitor cells that incorporate into endothelial cells or play a role in arteriogenesis compared with controls and patients with either progression of coronary atherosclerosis or stable disease.
我们前瞻性地研究经皮冠状动脉介入治疗时循环内皮祖细胞与支架内再狭窄或冠状动脉粥样硬化进展之间的关系。
内皮祖细胞为功能失调的内皮提供了一种内源性修复机制，因此在冠状动脉粥样硬化中可能发挥致病作用。
我们研究了 155 例稳定型心绞痛患者（92 例男性，年龄 60±11 岁）。所有患者均在择期经皮冠状动脉介入治疗前一天进行流式细胞术，以获得内皮祖细胞的亚群。考虑了 20 名正常对照者作为对照。
在 8 个月的对照血管造影中，30 例患者出现支架内再狭窄（再狭窄组），22 例患者出现冠状动脉粥样硬化进展（进展组），而其余 103 例患者既无支架内再狭窄也无冠状动脉粥样硬化进展（稳定组）。三组之间的比较在危险因素、心脏形态和功能、冠状动脉疾病的延伸以及治疗方面没有任何差异。再狭窄组（1.41±0.64 个/μl）测量的 CD34+/KDR+/CD45-细胞（即内皮谱系的祖细胞）绝对数量明显高于进展、稳定和对照组（1.03±0.53 个/μl、1.07±0.46 个/μl 和 0.95±0.44 个/μl，分别，p<0.05）。同样，CD133+/KDR+/CD45-细胞（即内皮细胞的早期祖细胞）在再狭窄组（0.63±0.23 个/μl）中也明显高于进展、稳定和对照组（0.33±0.19 个/μl、0.41±0.32 个/μl 和 0.36±0.15 个/μl，分别，p<0.001）。此外，CD14+/CD45+细胞（即通过旁分泌作用在血管生成中起作用的细胞）的数量在再狭窄、进展、稳定和对照组之间也有显著差异（0.72±0.56 个/μl 比 0.51±0.52 个/μl 比 0.28±0.54 个/μl 比 0.62±0.67 个/μl，分别，p<0.05），而 CD105+/CD45-/CD34-细胞（即转化生长因子-β的受体）在各组之间相似。
与对照组和冠状动脉粥样硬化进展或稳定的患者相比，再狭窄患者的内皮祖细胞亚群数量更高，这些亚群可整合到内皮细胞中或在动脉生成中发挥作用。
