Recruited macrophages elicit atrial fibrillation

Maarten Hulsmans, Maximilian J. Schloss, I. Hsiu Lee, Aneesh Bapat, Yoshiko Iwamoto, Claudio Vinegoni, Alexandre Paccalet, Masahiro Yamazoe, Jana Grune, Steffen Pabel, Noor Momin, Hana Seung, Nina Kumowski, Fadi E. Pulous, Daniel Keller, Constanze Bening, Ursula Green, Jochen K. Lennerz, Richard N. Mitchell, Andrew LewisBarbara Casadei, Oriol Iborra-Egea, Antoni Bayes-Genis, Samuel Sossalla, Chin Siang Ong, Richard N. Pierson, Jon C. Aster, David Rohde, Gregory R. Wojtkiewicz, Ralph Weissleder, Filip K. Swirski, George Tellides, George Tolis, Serguei Melnitchouk, David J. Milan, Patrick T. Ellinor, Kamila Naxerova, Matthias Nahrendorf

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


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.

Original languageEnglish
Pages (from-to)231-239
Number of pages9
Issue number6654
StatePublished - 14 Jul 2023


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