The CD14++CD16+ monocyte subset and monocyte-platelet interactions in patients with ST-elevation myocardial infarction
The CD14++CD16+ monocyte subset and monocyte-platelet interactions in patients with ST-elevation myocardial infarction
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DOI：
10.1111/j.1538-7836.2011.04603.x
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发表时间：
2012-07-01
影响因子：
10.4
通讯作者：
Lip, G. Y. H.
中科院分区：
文献类型：
--
作者：
Tapp, L. D.;Shantsila, E.;Lip, G. Y. H.
。目的：单核细胞通过子集异质性促进心肌损伤和修复。三种人类单核细胞亚群（包括独特的 CD14++CD16+ 亚群）的动力学和功能特征及其对 ST 段抬高型心肌梗死 (STEMI) 后单核细胞血小板聚集体 (MPA) 的贡献尚不清楚。我们的目的是检查 STEMI 后三种人类单核细胞亚群及其与血小板聚集的动态变化及其与左心室射血分数 (LVEF) 的关系。方法：通过流式细胞术分析 50 名 STEMI 患者、40 名稳定性冠状动脉疾病 (CAD) 患者和 40 名健康志愿者的三个单核细胞亚群 CD14++CD16-CCR2+（经典，Mon1）、CD14++CD16+CCR2+（中间，Mon2）和 CD14+CD16++CCR2-（非经典，Mon3）及其对 MPA 的贡献。研究参数在初次经皮冠状动脉介入治疗 (PCI)（第 1 天）24 小时内以及第 3、7 和 30 天进行测量。通过测量核因子 βB (NF?B) 途径评估单核细胞活化。 STEMI 后 6 周评估 LVEF。评估了单核细胞亚群/MPA 与血浆细胞因子和肌钙蛋白之间的相关性。结果：我们观察到子集动态存在显着差异，Mon2 显着增加 (P < 0.0001)，但 Mon3 没有变化。 Mon2 CD14 (P = 0.002) 和 CCR2 (P < 0.0001) 表达显着增加，CD16 表达减少 (P = 0.001)。 Mon2 中 NF?B 通路活性增加最为显着 (P = 0.007)。 Mon2 计数与肌钙蛋白峰值 (r = 0.31，P = 0.04)、血浆白细胞介素 (IL)-6 (r = 0.65，P < 0.0001) 和 IL-10 (r = 0.34，P = 0.017) 相关。 Mon1 与 IL-6 相关（r = 0.55，P < 0.0001）。第 1 天 CD16 Mon2 表达减少可独立预测较高的 LVEF（β = -0.37，P = 0.013）。 STEMI 后 MPA 计数的增加持续 1 个月。结论：Mon2中间子集在STEMI后具有独特的动态和功能特征，并且与肌钙蛋白、血浆细胞因子和恢复期左心室功能显着相关。 STEMI 后 30 天 MPA 计数持续增加可能会影响单核细胞亚群功能活动。
. Aim: Monocytes contribute to both myocardial damage and repair by virtue of subset heterogeneity. The dynamics and functional characteristics of the three human monocyte subsets, including the unique CD14++CD16+ subset, and their contributions to monocyte platelet aggregates (MPAs) following ST-elevation myocardial infarction (STEMI) are unknown. We aimed to examine dynamic changes and relation to left ventricular ejection fraction (LVEF) of the three human monocyte subsets and their aggregates with platelets following STEMI. Methods: Three monocyte subsets, CD14++CD16-CCR2+ (classical, Mon1), CD14++CD16+CCR2+ (intermediate, Mon2) and CD14+CD16++CCR2- (non-classical, Mon3), and their contribution to MPAs were analyzed by flow cytometry in 50 patients with STEMI, 40 patients with stable coronary artery disease (CAD) and 40 healthy volunteers. Study parameters were measured within 24 h of primary percutaneous coronary intervention (PCI) (day1) and on days 3, 7 and 30. Monocyte activation was assessed by measuring the nuclear factor ?B (NF?B) pathway. LVEF was assessed 6 weeks after STEMI. Correlations between monocyte subsets/MPAs and plasma cytokines and troponin were assessed. Results: We observed marked differences in subset dynamics, with a prominent increase in Mon2 (P < 0.0001) but no changes in Mon3. Significant increases in Mon2 CD14 (P = 0.002) and CCR2 (P < 0.0001) expression, and reduction in CD16 expression (P = 0.001) were seen. NF?B pathway activity increased most prominently in Mon2 (P = 0.007). Mon2 count correlated with peak troponin (r = 0.31, P = 0.04) and plasma interleukin (IL)-6 (r = 0.65, P < 0.0001) and IL-10 (r = 0.34, P = 0.017). Mon1 correlated with IL-6 (r = 0.55, P < 0.0001). Reduced Mon2 expression of CD16 on day 1 was independently predictive of higher LVEF (beta = -0.37, P = 0.013). The increase in MPA count following STEMI persisted at 1 month. Conclusion: The Mon2 intermediate subset has unique dynamic and functional characteristics following STEMI and significant correlations with troponin, plasma cytokines and convalescent left ventricular function. The persistent increase in MPA count 30 days after STEMI may affect monocyte subset functional activity.