Differential expression of Toll-like receptor 4 and human monocyte subsets in acute myocardial infarction

Objective: To investigate the involvement of Toll-like receptor 4 (TLR4) expression on two monocyte subsets in the pathologic processes related to acute coronary syndrome. How monocytes, which have recently been shown to comprise two distinct subsets, mediate the process of coronary plaque rupture remains to be fully elucidated. Recent studies have shown that TLR4 is involved in monocyte activation of patients with accelerated forms of atherosclerosis.Methods: We enrolled 65 patients with acute myocardial infarction (AMI, n = 22), unstable angina pectoris (UAP, n = 16), and stable angina pectoris (SAP, n = 27) who underwent coronary angiography and 15 healthy controls. The expression of TLR4 on two monocyte subsets (CD14(+)CD16(-) and CD14(+)CD16(+)) was measured by flow cytometry.Results: In patients with AMI, TLR4 was more expressed on circulating CD14(+)CD16(+) monocytes than on CD14(+)CD16(-) monocytes (p < 0.001). The expression levels of TLR4 on CD14(+)CD16(+) monocytes were significantly elevated in patients with AMI compared with other 3 groups. TLR4 expression levels on CD14(+)CD16(+) monocytes were significantly elevated at the culprit site compared with the systemic level (p = 0.044). The up-regulation of TLR4 on admission was remarkably decreased 12 days after AMI (p < 0.001). In addition, plasma levels of tumor necrosis factor-alpha were positively correlated with TLR4 expression levels on monocytes in patients with AMI (r = 0.47, p = 0.027).Conclusion: TLR overexpression on CD14(+)CD16(+) monocytes in AMI, as demonstrated both in the circulation and at the coronary culprit site, might be associated with the pathogenesis of AMI. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

目的：探讨Toll样受体4（TLR4）在两种单核细胞亚群上的表达在与急性冠状动脉综合征相关的病理过程中的作用。单核细胞最近被证明包含两种不同的亚群，它们如何介导冠状动脉斑块破裂的过程仍有待充分阐明。近期研究表明，TLR4参与加速型动脉粥样硬化患者的单核细胞活化。 方法：我们纳入了65例接受冠状动脉造影的患者，其中包括22例急性心肌梗死（AMI）患者、16例不稳定型心绞痛（UAP）患者和27例稳定型心绞痛（SAP）患者，以及15例健康对照者。通过流式细胞术检测两种单核细胞亚群（CD14⁺CD16⁻和CD14⁺CD16⁺）上TLR4的表达。 结果：在AMI患者中，循环中CD14⁺CD16⁺单核细胞上TLR4的表达高于CD14⁺CD16⁻单核细胞（p < 0.001）。与其他3组相比，AMI患者CD14⁺CD16⁺单核细胞上TLR4的表达水平显著升高。与全身水平相比，罪犯病变部位CD14⁺CD16⁺单核细胞上TLR4的表达水平显著升高（p = 0.044）。入院时TLR4的上调在AMI后12天显著降低（p < 0.001）。此外，AMI患者血浆肿瘤坏死因子 -α水平与单核细胞上TLR4的表达水平呈正相关（r = 0.47，p = 0.027）。 结论：如在循环中和冠状动脉罪犯病变部位所证实的，AMI中CD14⁺CD16⁺单核细胞上TLR的过度表达可能与AMI的发病机制有关。（C）2011爱思唯尔爱尔兰有限公司。保留所有权利。