Hulsmans, MaartenSchloss, Maximilian J.Lee, I-HsiuBapat, AneeshIwamoto, YoshikoVinegoni, ClaudioPaccalet, AlexandreYamazoe, MasahiroGrune, JanaPabel, SteffenMomin, NoorSeung, HanaKumowski, NinaPulous, FadiKeller, DanielBening, ConstanzeGreen, UrsulaLennerz, Jochen K.Mitchell, Richard N.Lewis, AndrewCasadei, BarbaraIborra-Egea, OriolBayes-Genis, AntoniSossalla, SamuelOng, Chin SiangPierson, Richard N.Aster, Jon C.Rohde, DavidWojtkiewicz, Gregory R.Weissleder, RalphSwirski, Filip K.Tellides, GeorgeTolis, GeorgeMelnitchouk, SergueiMilan, David J.Ellinor, Patrick T.Naxerova, KamilaNahrendorf, Matthias2023-08-14Maarten Hulsmans et al. ,Recruited macrophages elicit atrial fibrillation.Science381,231-239(2023).DOI:10.1126/science.abq3061https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37376756Atrial fibrillation disrupts contraction of the atria, leading to stroke and heart failure. We here decipher 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 crosstalk 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.en-USJournal Article2023-08-14