Recruited macrophages elicit atrial fibrillation.
Maarten HulsmansMaximilian J SchlossI-Hsiu LeeAneesh C BapatYoshiko IwamotoClaudio VinegoniAlexandre PaccaletMasahiro YamazoeJana GruneSteffen PabelNoor MominHana SeungNina KumowskiFadi E PulousDaniel KellerConstanze BeningUrsula GreenJochen K LennerzRichard N MitchellAndrew J M LewisBarabara CasadeiOriol Iborra-EgeaAntoni Bayés-GenísSamuel SossallaChin Siang OngRichard N PiersonJon C AsterDavid RohdeGregory R WojtkiewiczRalph WeisslederFilip K SwirskiGeorge TellidesGeorge TolisSerguei MelnitchoukDavid J MilanPatrick T EllinorKamila NaxerovaMatthias NahrendorfPublished in: Science (New York, N.Y.) (2023)
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.
Keyphrases
- atrial fibrillation
- single cell
- catheter ablation
- heart failure
- left atrial
- oral anticoagulants
- rna seq
- left atrial appendage
- direct oral anticoagulants
- mitral valve
- percutaneous coronary intervention
- high fat diet induced
- endothelial cells
- high throughput
- dendritic cells
- blood pressure
- gene expression
- metabolic syndrome
- cell therapy
- type diabetes
- adipose tissue
- chronic kidney disease
- brain injury
- signaling pathway
- physical activity
- oxidative stress
- immune response
- ejection fraction
- weight loss
- blood brain barrier
- newly diagnosed
- prognostic factors
- left ventricular
- body mass index
- peripheral blood
- pluripotent stem cells