Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Tokyo New Drug Research Laboratories, Kowa Company, Ltd., Tokyo, Japan.
PLoS One. 2020 Oct 13;15(10):e0240540. doi: 10.1371/journal.pone.0240540. eCollection 2020.
Pathophysiological roles of monocytes in atrial fibrillation (AF), particularly for the progression of structural remodeling of the left atrium (LA), remain elusive. This study examined the association between the characteristics of circulating and local monocytes and extent of structural remodeling in LA, gauged by LA size, in AF patients.
First, 161 AF patients who were referred for catheter ablation were enrolled and divided into two groups according to the median of LA diameter (≤39 mm: normal LA group, >39 mm: enlarged LA group). As a control group, 22 patients underwent catheter ablation for paroxysmal supraventricular tachycardia (PSVT) without history of AF were analyzed. Blood samples were collected for flow cytometric analyses to evaluate monocyte subsets based on the levels of CD14 and CD16. Moreover, monocytes were isolated from blood to measure CC chemokine receptor 2 (CCR2) transcripts and protein levels, and migratory activity toward monocyte chemoattractant protein 1 (MCP-1). Second, to characterize the local monocytes in the atrial wall in AF, the resected left atrial appendages (LAA) in AF patients underwent cardiac surgery were histologically evaluated (n = 20).
The proportions of monocyte subsets based on CD14 and CD16 expressions were not significantly different between the normal and enlarged LA group. Both transcripts and total protein levels of CCR2 in monocytes were higher in the enlarged LA group compared to those in the normal LA group. In the enlarged LA group, monocytes exhibited more enhanced migratory activity than the normal LA group. Moreover, we found a significantly higher number of CCR2-positive monocytes/macrophages in the LAA in the enlarged LA group.
Enhanced migratory activity in circulating and local monocytes may play a pivotal role in the pathogenesis of progression in atrial remodeling in AF patients.
单核细胞在心房颤动（AF）中的病理生理作用，尤其是对左心房（LA）结构重构的进展，仍然难以捉摸。本研究检测了循环和局部单核细胞的特征与 AF 患者 LA 结构重构程度（通过 LA 大小评估）之间的相关性。
首先，纳入了 161 例因导管消融而就诊的 AF 患者，并根据 LA 直径的中位数（≤39mm：正常 LA 组，>39mm：LA 扩大组）将其分为两组。作为对照组，分析了 22 例因阵发性室上性心动过速（PSVT）而接受导管消融且无 AF 病史的患者。采集血液样本进行流式细胞术分析，根据 CD14 和 CD16 水平评估单核细胞亚群。此外，从血液中分离单核细胞以测量趋化因子受体 2（CCR2）转录本和蛋白水平以及对单核细胞趋化蛋白 1（MCP-1）的迁移活性。其次，为了描述 AF 患者左心耳（LAA）心房壁中的局部单核细胞，对接受心脏手术的 AF 患者的 LAA 进行了组织学评估（n=20）。
正常 LA 组和 LA 扩大组之间基于 CD14 和 CD16 表达的单核细胞亚群比例没有显著差异。与正常 LA 组相比，LA 扩大组的单核细胞中 CCR2 的转录本和总蛋白水平均较高。在 LA 扩大组中，单核细胞的迁移活性明显高于正常 LA 组。此外，我们发现 LA 扩大组的 LAA 中 CCR2 阳性单核细胞/巨噬细胞数量明显较高。
循环和局部单核细胞中增强的迁移活性可能在 AF 患者心房重构进展的发病机制中起关键作用。
