Recruited macrophages elicit atrial fibrillation
成果类型：
Article
署名作者：
Hulsmans, Maarten; Schloss, Maximilian J.; Lee, I-Hsiu; Bapat, Aneesh; Iwamoto, Yoshiko; Vinegoni, Claudio; Paccalet, Alexandre; Yamazoe, Masahiro; Grune, Jana; Pabel, Steffen; Momin, Noor; Seung, Hana; Kumowski, Nina; Pulous, Fadi E.; Keller, Daniel; Bening, Constanze; Green, Ursula; Lennerz, Jochen K.; Mitchell, Richard N.; Lewis, Andrew; Casadei, Barbara; Iborra-Egea, Oriol; Bayes-Genis, Antoni; Sossalla, Samuel; Ong, Chin Siang; Pierson, Richard N.; Aster, Jon C.; Rohde, David; Wojtkiewicz, Gregory R.; Weissleder, Ralph; Swirski, Filip K.; Tellides, George; Tolis, George, Jr.; Melnitchouk, Serguei; Milan, David J.; Ellinor, Patrick T.; Naxerova, Kamila; Nahrendorf, Matthias
署名单位：
Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; University of Regensburg; University of Wurzburg; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; University of Oxford; University of Oxford; CIBER - Centro de Investigacion Biomedica en Red; CIBERCV; Justus Liebig University Giessen; German Centre for Cardiovascular Research; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Yale University; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University of Wurzburg
刊物名称：
SCIENCE
ISSN/ISSBN：
0036-8830
DOI：
10.1126/science.abq3061
发表日期：
2023-07-14
页码：
231-238
关键词：
angiotensin-ii
cardiac macrophages
osteopontin
fibrosis
expression
atherosclerosis
inflammation
activation
mechanisms
cells
摘要：
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 Ccr(2-/-) 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.