Epicardial Fat Drives Macrophage Response in Atrial Cardiomyopathy.

Abstract

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. 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. These data highlight the pivotal role of macrophages in atrial adiposity, in particular that of Lyve1⁺-macrophages during adipose tissue expansion.