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Open Access 01-12-2023 | Atrial Fibrillation | Research

Atrial epicardial adipose tissue abundantly secretes myeloperoxidase and activates atrial fibroblasts in patients with atrial fibrillation

Authors: Eva R. Meulendijks, Rushd F. M. Al-Shama, Makiri Kawasaki, Benedetta Fabrizi, Jolien Neefs, Robin Wesselink, Auriane C. Ernault, Sander Piersma, Thang V. Pham, Connie R. Jimenez, Jaco C. Knol, Wim J. P. van Boven, Antoine H. G. Driessen, Tim A. C. de Vries, Britt van der Leeden, Hans W. M. Niessen, Onno J. de Boer, Sébastien P. J. Krul, Joris R. de Groot

Published in: Journal of Translational Medicine | Issue 1/2023

Abstract

Background

Epicardial adipose tissue (EAT) secretome induces fibrosis. Fibrosis, primarily extracellular matrix (ECM) produced by fibroblasts, creates a substrate for atrial fibrillation (AF). Whether the EAT secretome from patients with AF activates human atrial fibroblasts and through which components, remains unexplored.

Research aims

(a) To investigate if the EAT secretome from patients with versus without AF increases ECM production in atrial fibroblasts. (b) To identify profibrotic proteins and processes in the EAT secretome and EAT from patients with, who will develop (future onset), and without AF.

Methods

Atrial EAT was obtainded during thoracoscopic ablation (AF, n = 20), or open-heart surgery (future onset and non-AF, n = 35). ECM gene expression of human atrial fibroblasts exposed to the EAT secretome and the proteomes of EAT secretome and EAT were assessed in patients with and without AF. Myeloperoxidase and neutrophil extracellular traps (NETs) were assessed immunohistochemically in patients with paroxysmal, persistent, future onset, and those who remain free of AF (non-AF).

Results

The expression of COL1A1 and FN1 in fibroblasts exposed to secretome from patients with AF was 3.7 and 4.7 times higher than in patients without AF (p < 0.05). Myeloperoxidase was the most increased protein in the EAT secretome and EAT from patients with versus without AF (FC 18.07 and 21.57, p < 0.005), as was the gene-set neutrophil degranulation. Immunohistochemically, myeloperoxidase was highest in persistent (FC 13.3, p < 0.0001) and increased in future onset AF (FC 2.4, p = 0.02) versus non-AF. Myeloperoxidase aggregated subepicardially and around fibrofatty infiltrates. NETs were increased in patients with persistent versus non-AF (p = 0.03).

Conclusion

In AF, the EAT secretome induces ECM gene expression in atrial fibroblasts and contains abundant myeloperoxidase. EAT myeloperoxidase was increased prior to AF onset, and both myeloperoxidase and NETs were highest in persistent AF, highlighting the role of EAT neutrophils in the pathophysiology of AF.

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Y Egami MN, J Tanouchi (2015) Relation Between Colchicine and Epicardial Adipose Tissue Volume Surrounding Left Atrium in Atrial Fibrillation Recurrence After Ablation. In:SESSION TITLE: TREATMENT OF ARRHYTHMIAS: PHARMACOLOGIC II, Circulation

Title: Atrial epicardial adipose tissue abundantly secretes myeloperoxidase and activates atrial fibroblasts in patients with atrial fibrillation
Authors: Eva R. Meulendijks
Rushd F. M. Al-Shama
Makiri Kawasaki
Benedetta Fabrizi
Jolien Neefs
Robin Wesselink
Auriane C. Ernault
Sander Piersma
Thang V. Pham
Connie R. Jimenez
Jaco C. Knol
Wim J. P. van Boven
Antoine H. G. Driessen
Tim A. C. de Vries
Britt van der Leeden
Hans W. M. Niessen
Onno J. de Boer
Sébastien P. J. Krul
Joris R. de Groot
Publication date: 01-12-2023
Publisher: BioMed Central
Keyword: Atrial Fibrillation
Published in: Journal of Translational Medicine / Issue 1/2023
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-023-04231-2

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