TherapeuticSpp1silencing in TREM2+cardiac macrophages suppresses atrial fibrillation

Abstract

AbstractAtrial fibrillation (AFib) and the risk of its lethal complications are propelled by fibrosis, which induces electrical heterogeneity and gives rise to reentry circuits. Atrial TREM2+macrophages secrete osteopontin (encoded bySpp1), a matricellular signaling protein that engenders fibrosis and AFib. Here we show that silencingSpp1in TREM2+cardiac macrophages with an antibody-siRNA conjugate reduces atrial fibrosis and suppresses AFib in mice, thus offering a new immunotherapy for the most common arrhythmia.