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Recruited macrophages elicit atrial fibrillation.

Maarten HulsmansMaximilian J SchlossI-Hsiu LeeAneesh C BapatYoshiko IwamotoClaudio VinegoniAlexandre PaccaletMasahiro YamazoeJana GruneSteffen PabelNoor MominHana SeungNina KumowskiFadi E PulousDaniel KellerConstanze BeningUrsula GreenJochen K LennerzRichard N MitchellAndrew J M LewisBarabara CasadeiOriol Iborra-EgeaAntoni Bayés-GenísSamuel SossallaChin Siang OngRichard N PiersonJon C AsterDavid RohdeGregory R WojtkiewiczRalph WeisslederFilip K SwirskiGeorge TellidesGeorge TolisSerguei MelnitchoukDavid J MilanPatrick T EllinorKamila NaxerovaMatthias Nahrendorf
Published in: Science (New York, N.Y.) (2023)
Atrial fibrillation disrupts contraction of the atria, leading to stroke and heart failure. We deciphered how immune and stromal cells contribute to atrial fibrillation. Single-cell transcriptomes from human atria documented inflammatory monocyte and SPP1 + macrophage expansion in atrial fibrillation. Combining hypertension, obesity, and mitral valve regurgitation (HOMER) in mice elicited enlarged, fibrosed, and fibrillation-prone atria. Single-cell transcriptomes from HOMER mouse atria recapitulated cell composition and transcriptome changes observed in patients. Inhibiting monocyte migration reduced arrhythmia in Ccr2 -∕- HOMER mice. Cell-cell interaction analysis identified SPP1 as a pleiotropic signal that promotes atrial fibrillation through cross-talk with local immune and stromal cells. Deleting Spp1 reduced atrial fibrillation in HOMER mice. These results identify SPP1 + macrophages as targets for immunotherapy in atrial fibrillation.
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