Recruited macrophages elicit atrial fibrillation

Science. 2023 Jul 14;381(6654):231-239. doi: 10.1126/science.abq3061. Epub 2023 Jul 13.


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.

MeSH terms

  • Animals
  • Atrial Fibrillation* / genetics
  • Atrial Fibrillation* / immunology
  • Cell Movement
  • Gene Deletion
  • Heart Atria
  • Humans
  • Macrophages* / immunology
  • Mice
  • Mitral Valve Insufficiency / genetics
  • Osteopontin* / genetics
  • Single-Cell Gene Expression Analysis


  • Spp1 protein, mouse
  • Osteopontin
  • SPP1 protein, human