Recruited macrophages elicit atrial fibrillation

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…

• AH
  American Heart Association

  Awards: HL092577, 18SFRN34110082, MAESTRIA 965286
• P
  Pfizer
• B
  Biogen
• AP
  Alnylam Pharmaceuticals
• CB
  CSL Behring
• NI
  National Institute for Health and Care Research
• BH
  British Heart Foundation
• EC
  European Commission

  Awards: MAESTRIA 965286, 965286
• DF
  Deutsche Forschungsgemeinschaft

  Awards: SFB 1525, 453989101, 965286
• S
  Servier
• NI
  National Institutes of Health

  Awards: HL142494, DK040561, CA225655, 18SFRN34110082, HL092577, HL139598, 965286
• HS
  Harvard Stem Cell Institute
• NO
  NIHR Oxford Biomedical Research Centre