Cardiology Department, Thorax Institute, Hospital Clínic, IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
Neurology Department, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), DCEXS Universitat Pompeu Fabra, Barcelona, Spain.
J Mol Cell Cardiol. 2015 Mar;80:146-55. doi: 10.1016/j.yjmcc.2015.01.005. Epub 2015 Jan 22.
The mobilization pattern and functionality of endothelial progenitor cells after an acute ischemic event remain largely unknown. The aim of our study was to characterize and compare the short- and long-term mobilization of endothelial progenitor cells and circulating endothelial cells after acute myocardial infarction or atherothrombotic stroke, and to determine the relationship between these cell counts and plasma concentrations of vascular cell adhesion molecule (VCAM-1) and Von Willebrand factor (VWF) as surrogate markers of endothelial damage and inflammation. In addition, we assessed whether endothelial progenitor cells behave like functional endothelial cells. We included 150 patients with acute myocardial infarction or atherothrombotic stroke and 145 controls. Endothelial progenitor cells [CD45-, CD34+, KDR+, CD133+], circulating endothelial cells [CD45-, CD146+, CD31+], VWF, and VCAM-1 levels were measured in controls (baseline only) and in patients within 24h (baseline) and at 7, 30, and 180 days after the event. Myocardial infarction patients had higher counts of endothelial progenitor cells and circulating endothelial cells than the controls (201.0/mL vs. 57.0/mL; p<0.01 and 181.0/mL vs. 62.0/mL; p<0.01). Endothelial progenitor cells peaked at 30 days post-infarction (201.0/mL vs. 369.5/mL; p<0.01), as did VCAM-1 (573.7 ng/mL vs. 701.8 ng/mL; p<0.01). At 180 days post-infarction, circulating endothelial cells and VWF decreased, compared to baseline. In stroke patients, the number of endothelial progenitor cells - but not circulating endothelial cells - was higher than in controls (90.0/mL vs. 37.0/mL; p=0.01; 105.0/mL vs. 71.0/mL; p=0.11). At 30 days after stroke, however, VCAM-1 peaked (628.1/mL vs. 869.1/mL; p<0.01) but there was no significant change in endothelial progenitor cells (90/mL vs. 78/mL; p<0.34). At 180 days after stroke, circulating endothelial cells and VWF decreased, compared to baseline. Cultured endothelial progenitor cells from controls and myocardial infarction patients had endothelial phenotype characteristics and exhibited functional differences in adhesion and Ca(2+) influx, but not in proliferation and vasculogenesis. In myocardial infarction patients, VCAM-1 levels and mobilization of endothelial progenitor cells peaked at 30 days after the ischemic event. Although a similar VCAM-1 kinetic was observed in stroke patients, endothelial progenitor cells did not increase. Endothelial progenitor cells had mature endothelial capabilities in vitro.
急性缺血事件后内皮祖细胞的动员模式和功能在很大程度上仍然未知。我们的研究目的是描述和比较急性心肌梗死或动脉血栓性卒中后内皮祖细胞和循环内皮细胞的短期和长期动员，并确定这些细胞计数与血管细胞黏附分子（VCAM-1）和血管性血友病因子（VWF）的血浆浓度之间的关系，作为内皮损伤和炎症的替代标志物。此外，我们评估了内皮祖细胞是否表现为功能性内皮细胞。我们纳入了 150 例急性心肌梗死或动脉血栓性卒中患者和 145 例对照者。在对照者（仅基线）和患者中于事件后 24 小时内（基线）以及 7、30 和 180 天时测量内皮祖细胞[CD45-，CD34+，KDR+，CD133+]、循环内皮细胞[CD45-，CD146+，CD31+]、VWF 和 VCAM-1 水平。心肌梗死患者的内皮祖细胞和循环内皮细胞计数高于对照者（201.0/mL 比 57.0/mL；p<0.01 和 181.0/mL 比 62.0/mL；p<0.01）。内皮祖细胞在梗死 30 天时达到峰值（201.0/mL 比 369.5/mL；p<0.01），VCAM-1 也是如此（573.7 ng/mL 比 701.8 ng/mL；p<0.01）。在梗死 180 天时，与基线相比，循环内皮细胞和 VWF 降低。在卒中患者中，内皮祖细胞的数量-但不是循环内皮细胞-高于对照者（90.0/mL 比 37.0/mL；p=0.01；105.0/mL 比 71.0/mL；p=0.11）。然而，在卒中后 30 天时，VCAM-1 达到峰值（628.1/mL 比 869.1/mL；p<0.01），但内皮祖细胞没有明显变化（90/mL 比 78/mL；p<0.34）。在卒中后 180 天时，与基线相比，循环内皮细胞和 VWF 降低。来自对照者和心肌梗死患者的培养内皮祖细胞具有内皮表型特征，并表现出黏附和 Ca（2+）内流的功能差异，但增殖和血管生成无差异。在心肌梗死患者中，VCAM-1 水平和内皮祖细胞动员在缺血事件后 30 天达到峰值。尽管在卒中患者中观察到类似的 VCAM-1 动力学，但内皮祖细胞没有增加。内皮祖细胞在体外具有成熟的内皮细胞功能。
