TGFβ Is Specifically Upregulated on Circulating CD14++ CD16+ and CD14+ CD16++ Monocytes in Patients with Atrial Fibrillation and Severe Atrial Fibrosis
TGFβ Is Specifically Upregulated on Circulating CD14++ CD16+ and CD14+ CD16++ Monocytes in Patients with Atrial Fibrillation and Severe Atrial Fibrosis
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DOI：
10.1159/000492873
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Seizer, Peter
中科院分区：
文献类型：
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作者：
Heinzmann, David;Fuss, Stefan;Seizer, Peter
背景/目的：心房纤维化重构在房颤（AF）的发病机制中起关键作用。由于对循环单核细胞在心房重构和房颤病理生理中的作用知之甚少，我们研究了心房颤动导管消融患者不同亚群循环单核细胞的促纤维化因子。方法：对71例持续性房颤患者进行窦性心律三维高密度电压测图，评价其心房低压区（LVAs）的范围，以窦性心律< 0.5mV的信号为低压。消融前抽血，流式细胞仪分析单核细胞。基于CD14和CD16的表达，我们分析了CD14(++) CD16(-)（“经典”）、CD14(++) CD16(+)（“中间”）和CD14(+) CD16(++)（“非经典”）三个亚组中TGF β、CD147和MMP-9的表达，这些亚组代表了心肌重构中关键的纤维化途径。结果：与低延伸LVAs患者相比，广泛LVAs患者CD14（+）单核细胞中TGFb的表达增加。而CD14(++) CD16（-）单核细胞没有差异，CD14(++) CD16（+）和CD14(+) CD16（++）单核细胞表现出TGFb丰度的强烈增加。尽管CD147和MMP-9与心肌纤维化密切相关，但我们发现两组在任何单核细胞亚群中的表达均无差异。结论：在广泛LVAs行导管消融的患者中，TGFb在CD14(++) CD16（+）和CD14(+) CD16（++）单核细胞上特异性上调。(C) 2018作者：s . Karger AG，巴塞尔出版
Background/Aims: Fibrotic remodeling of the atria plays a key role in the pathogenesis of atrial fibrillation (AF). As little is known about the contribution of circulating monocytes in atrial remodeling and the pathophysiology of AF, we investigated profibrotic factors in different subsets of circulating monocytes obtained from patients with atrial fibrillation undergoing catheter ablation. Methods: A 3D high density voltage mapping was performed in sinus rhythm to evaluate the extent of low-voltage areas (LVAs) in the atria of 71 patients with persistent AF. Low-voltage was defined as signals of < 0.5mV during sinus rhythm. Prior to ablation, blood was drawn and monocytes were analyzed by FACS. Based on the expression of CD14 and CD16, three subgroups including CD14(++) CD16(-) ('classical'), CD14(++) CD16(+) ('intermediate'), and CD14(+) CD16(++) ('non-classical') were analyzed for the expression of TGF beta, CD147, and MMP-9, representing pivotal profibrotic pathways in myocardial remodeling. Results: Expression of TGFb was increased in CD14(+) monocytes of patients with extensive LVAs compared to patients with a low extend of LVAs. While CD14(++) CD16(-) monocytes showed no difference, CD14(++) CD16(+) and CD14(+) CD16(++) monocytes showed a strong increase of TGFb abundance. Although CD147 and MMP-9 are strongly associated with myocardial fibrosis, we found no difference in expression between the two groups in any monocyte subsets. Conclusion: TGFb is specifically upregulated on CD14(++) CD16(+) and CD14(+) CD16(++) monocytes in patients with extensive LVAs undergoing catheter ablation. (C) 2018 The Author(s) Published by S. Karger AG, Basel