Depleting CCR2+ macrophages in obese mice prevented fibro-fatty remodeling, atrial dilation, and atrial fibrillation, while depleting Lyve1+ macrophages prevented early fat expansion.
Does macrophage depletion prevent fibro-fatty remodeling and atrial fibrillation in a mouse model of obesity and atrial cardiomyopathy?
This study identifies distinct roles for macrophage subpopulations in atrial adiposity and remodeling, suggesting CCR2+ macrophages as a potential therapeutic target to prevent atrial fibrillation.
BACKGROUND: Inflammation is associated with atrial fibrillation, but its precise impact on the long-term progression of the atrial fibrillation substrate, also called atrial cardiomyopathy, remains debated. METHODS AND RESULTS: Here, using spatial gene expression analysis, macrophage subpopulations mainly confined to the epicardial fat tissue were identified in the human atria. In a mouse model of obesity and atrial cardiomyopathy, macrophage recruitment was associated with atrial adiposity. Single-cell RNA sequencing allowed the identification of Lyve1 + -resident and CCR2 + monocyte-derived macrophages in obese mouse atria. In obese mice, depleting Lyve1 + -macrophages prevented early fat expansion and led to myocardial dystrophy, while CCR2 + -macrophage depletion prevented fibro-fatty remodeling, atrial dilation, and atrial fibrillation. CONCLUSIONS: These data highlight the pivotal role of macrophages in atrial adiposity, in particular that of Lyve1 + -macrophages during adipose tissue expansion.
This Circulation Research paper provides new mechanistic insights into the role of epicardial fat and inflammation in the development of the substrate for atrial fibrillation.
Crépin et al. (Fri,) conducted a other in Atrial cardiomyopathy and obesity. Macrophage depletion (Lyve1+ and CCR2+) was evaluated on Fibro-fatty remodeling, atrial dilation, and atrial fibrillation. Depleting CCR2+ macrophages in obese mice prevented fibro-fatty remodeling, atrial dilation, and atrial fibrillation, while depleting Lyve1+ macrophages prevented early fat expansion.