Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
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 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 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 reduced atrial fibrillation in HOMER mice. These results identify SPP1 macrophages as targets for immunotherapy in atrial fibrillation.
心房颤动扰乱了心房的收缩，导致中风和心力衰竭。我们破解了免疫细胞和基质细胞如何导致心房颤动。来自人类心房的单细胞转录组记录了心房颤动中炎症性单核细胞和巨噬细胞的扩张。在小鼠中结合高血压、肥胖和二尖瓣反流（HOMER），可引起心房扩大、纤维化和易发生颤动。来自 HOMER 小鼠心房的单细胞转录组再现了在患者中观察到的细胞组成和转录组变化。抑制单核细胞迁移可减少 HOMER 小鼠的心律失常。细胞间相互作用分析确定 SPP1 是一种多效信号，通过与局部免疫和基质细胞的相互作用促进心房颤动。删除 SPP1 减少了 HOMER 小鼠的心房颤动。这些结果确定 SPP1 巨噬细胞是心房颤动免疫治疗的靶点。
