Key result
The epicardial adipose tissue secretome from patients with atrial fibrillation induced 3.7 and 4.7 times higher COL1A1 and FN1 gene expression in atrial fibroblasts and contained abundantly increased myeloperoxidase compared to patients without atrial fibrillation.
Why the study?
Whether the epicardial adipose tissue secretome from patients with AF activates human atrial fibroblasts and through which components remained unexplored.
Does epicardial adipose tissue secretome from patients with atrial fibrillation increase profibrotic gene expression in atrial fibroblasts compared to secretome from patients without atrial fibrillation?
Observational (n=55)
Yes
Does epicardial adipose tissue secretome from patients with atrial fibrillation increase profibrotic gene expression in atrial fibroblasts compared to secretome from patients without atrial fibrillation?
Effect estimate: 3.7 and 4.7 times higher
p-value: p=<0.05
Epicardial adipose tissue from patients with atrial fibrillation secretes abundant myeloperoxidase and directly induces profibrotic gene expression in atrial fibroblasts, suggesting a neutrophil-driven mechanism for atrial structural remodeling.
EAT myeloperoxidase may promote atrial fibroblast activation in AF; leaves open whether neutrophil-targeted interventions modify fibrosis or AF risk.
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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Meulendijks et al. (2023) conducted an observational in Atrial fibrillation (n=55). Atrial fibrillation (EAT secretome) vs. Patients without atrial fibrillation was evaluated on COL1A1 and FN1 expression in atrial fibroblasts exposed to EAT secretome (3.7 and 4.7 times higher, p=<0.05). The epicardial adipose tissue secretome from patients with atrial fibrillation induced 3.7 and 4.7 times higher COL1A1 and FN1 gene expression in atrial fibroblasts and contained abundantly increased myeloperoxidase compared to patients without atrial fibrillation.
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