Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, University Tübingen, Tübingen, Germany.
Eur Heart J. 2014 Feb;35(6):386-94. doi: 10.1093/eurheartj/eht448. Epub 2013 Oct 29.
Surface expression of stromal cell-derived factor-1 (SDF-1) on platelets is enhanced during ischaemic events and might play an important role in peripheral homing and myocardial repair. As SDF-1 effects are mediated through CXCR4/CXCR7, we investigated platelet expression of SDF-1/CXCR4/CXCR7 in patients with coronary artery disease (CAD).
Expression of SDF-1, CXCR4, and CXCR7 in platelets was investigated by western blot analysis, immunofluorescence confocal microscopy, and flow cytometry among healthy subjects and patients with acute coronary syndrome (ACS) and stable CAD. In a cohort study, platelet surface expression of CXCR4, CXCR7, and SDF-1 was measured in 215 patients with symptomatic CAD (stable CAD = 112, ACS = 103) at the time of percutaneous coronary intervention. Course of left ventricular ejection fraction (LVEF) was followed up during intrahospital stay and at 3 months. Both CXCR4 and CXCR7 are surface expressed on human platelets and to a higher degree in CAD patients when compared with healthy controls. Platelet surface expression of CXCR7 but not CXCR4 was enhanced in patients with ACS when compared with patients with stable CAD (mean fluorescence intensity 17.8 vs. 15.3, P = 0.004 and 29.0 vs. 26.3, P = 0.122, respectively). CXCR4 and CXCR7 significantly correlated with their ligand SDF-1 on platelets (ρ = 0.273, P < 0.001 and ρ = 0.454, P < 0.001, respectively). Additionally, high CXCR7 expression above the median correlated with the absolute improvement of LVEF% after 5 days and 3 months (46.2, 49.8, 53.7; P = 0.003).
These findings indicate that platelet surface expression of CXCR4 and CXCR7 might differentially contribute to SDF-1-mediated effects on regenerative mechanisms following ACS. Studies are warranted to further evaluate the regulatory mechanisms of CXCR4/-7 expression and its prognostic impact on CAD.
血小板表面基质细胞衍生因子-1（SDF-1）的表达在缺血事件中增强，可能在周围归巢和心肌修复中发挥重要作用。由于 SDF-1 作用是通过 CXCR4/CXCR7 介导的，我们研究了冠心病（CAD）患者血小板中 SDF-1/CXCR4/CXCR7 的表达。
通过 Western blot 分析、免疫荧光共聚焦显微镜和流式细胞术，在健康受试者和急性冠状动脉综合征（ACS）和稳定型 CAD 患者中研究了 SDF-1、CXCR4 和 CXCR7 在血小板中的表达。在一项队列研究中，在经皮冠状动脉介入治疗时测量了 215 例有症状 CAD 患者（稳定型 CAD = 112，ACS = 103）的血小板表面 CXCR4、CXCR7 和 SDF-1 表达。在住院期间和 3 个月时随访左心室射血分数（LVEF）的变化。人类血小板表面表达 CXCR4 和 CXCR7，且 CAD 患者的表达程度高于健康对照组。与稳定型 CAD 患者相比，ACS 患者的血小板表面 CXCR7 表达增强（平均荧光强度分别为 17.8 比 15.3，P = 0.004 和 29.0 比 26.3，P = 0.122）。CXCR4 和 CXCR7 与血小板上的配体 SDF-1 显著相关（ρ=0.273，P <0.001 和 ρ=0.454，P <0.001）。此外，中位数以上的高 CXCR7 表达与 5 天和 3 个月后 LVEF%的绝对改善相关（46.2、49.8、53.7；P = 0.003）。
这些发现表明，血小板表面 CXCR4 和 CXCR7 的表达可能对 ACS 后再生机制中 SDF-1 介导的作用有不同的贡献。有必要进行进一步研究以评估 CXCR4/-7 表达的调节机制及其对 CAD 的预后影响。
