Enhanced monocyte migratory activity in the pathogenesis of structural remodeling in atrial fibrillation

PLoS One. 2020 Oct 13;15(10):e0240540. doi: 10.1371/journal.pone.0240540. eCollection 2020.

Abstract

Background and aims: 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.

Methods: 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).

Results: 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.

Conclusion: Enhanced migratory activity in circulating and local monocytes may play a pivotal role in the pathogenesis of progression in atrial remodeling in AF patients.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atrial Fibrillation / blood
  • Atrial Fibrillation / physiopathology*
  • Atrial Fibrillation / surgery
  • Atrial Remodeling / physiology*
  • Case-Control Studies
  • Catheter Ablation
  • Chemotaxis*
  • Disease Progression
  • Female
  • Flow Cytometry
  • Humans
  • Male
  • Middle Aged
  • Monocytes / physiology*
  • Tachycardia, Ventricular / blood
  • Tachycardia, Ventricular / surgery

Grant support

This work was supported by a Grant for Cross-disciplinary Collaboration, Juntendo University to KM, HI, HD (30-13, https://www.juntendo.ac.jp). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. One of the authors, Katsutoshi Miyosawa, is employed by a commercial company, Kowa Company, Ltd. The funder (Kowa Company, Ltd.) provided support in the form of salaries for author [KM], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of the author is articulated in the ‘author contributions’ section.