Recruited macrophages elicit atrial fibrillation

Maarten Hulsmans(Harvard University), Maximilian J. Schloss(Harvard University), I‐Hsiu Lee(Harvard University), Aneesh Bapat(Harvard University), Yoshiko Iwamoto(Harvard University), Claudio Vinegoni(Harvard University), Alexandre Paccalet(Harvard University), Masahiro Yamazoe(Harvard University), Jana Grune(Harvard University), Steffen Pabel(Harvard University), Noor Momin(Harvard University), Hana Seung(Harvard University), Nina Kumowski(Harvard University), Fadi E. Pulous(Harvard University), Daniel M. Keller(Universitätsklinikum Würzburg), C. Bening(Universitätsklinikum Würzburg), Ursula Green(Harvard University), Jochen K. Lennerz(Harvard University), Richard N. Mitchell(Brigham and Women's Hospital), Andrew Lewis(British Heart Foundation), Barbara Casadei(British Heart Foundation), Oriol Iborra‐Egea(Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol), Antoni Bayés‐Genís(Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol), Samuel Sossalla(German Centre for Cardiovascular Research), Chin Siang Ong(Harvard University), Richard N. Pierson(Harvard University), Jon C. Aster(Brigham and Women's Hospital), David Rohde(Harvard University), Gregory R. Wojtkiewicz(Harvard University), Ralph Weissleder(Harvard University), Filip K. Świrski(Icahn School of Medicine at Mount Sinai), George Tellides(Yale University), George Tolis(Brigham and Women's Hospital), Serguei Melnitchouk(Harvard University), David J. Milan(Boston Foundation), Patrick T. Ellinor(Broad Institute), Kamila Naxerova(Harvard University), Matthias Nahrendorf(Harvard University)
Science
July 13, 2023
10.1126/science.abq3061
Cited by 202Open Access
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Abstract

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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