Noor Momin, Steffen Pabel, Arnab Rudra, Nina Kumowski, I-Hsiu Lee, Kyle Mentkowski, Masahiro Yamazoe, Laura Stengel, Charlotte G. Muse, Hana Seung, Alexandre Paccalet, Cristina Gonzalez-Correa, Emily B. Jacobs, Jana Grune, Maximilian J. Schloss, Samuel Sossalla, Gregory Wojtkiewicz, Yoshiko Iwamoto, Patrick McMullen, Richard N. Mitchell, Patrick T. Ellinor, Daniel G. Anderson, Kamila Naxerova, Matthias Nahrendorf, Maarten Hulsmans
{"title":"Therapeutic Spp1 silencing in TREM2+ cardiac macrophages suppresses atrial fibrillation","authors":"Noor Momin, Steffen Pabel, Arnab Rudra, Nina Kumowski, I-Hsiu Lee, Kyle Mentkowski, Masahiro Yamazoe, Laura Stengel, Charlotte G. Muse, Hana Seung, Alexandre Paccalet, Cristina Gonzalez-Correa, Emily B. Jacobs, Jana Grune, Maximilian J. Schloss, Samuel Sossalla, Gregory Wojtkiewicz, Yoshiko Iwamoto, Patrick McMullen, Richard N. Mitchell, Patrick T. Ellinor, Daniel G. Anderson, Kamila Naxerova, Matthias Nahrendorf, Maarten Hulsmans","doi":"10.1101/2024.08.10.607461","DOIUrl":null,"url":null,"abstract":"Atrial fibrillation (AFib) and the risk of its lethal complications are propelled by fibrosis, which induces electrical heterogeneity and gives rise to reentry circuits. Atrial TREM2+ macrophages secrete osteopontin (encoded by Spp1), a matricellular signaling protein that engenders fibrosis and AFib. Here we show that silencing Spp1 in TREM2+ cardiac macrophages with an antibody-siRNA conjugate reduces atrial fibrosis and suppresses AFib in mice, thus offering a new immunotherapy for the most common arrhythmia.","PeriodicalId":501182,"journal":{"name":"bioRxiv - Immunology","volume":"43 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"bioRxiv - Immunology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.08.10.607461","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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Abstract
Atrial fibrillation (AFib) and the risk of its lethal complications are propelled by fibrosis, which induces electrical heterogeneity and gives rise to reentry circuits. Atrial TREM2+ macrophages secrete osteopontin (encoded by Spp1), a matricellular signaling protein that engenders fibrosis and AFib. Here we show that silencing Spp1 in TREM2+ cardiac macrophages with an antibody-siRNA conjugate reduces atrial fibrosis and suppresses AFib in mice, thus offering a new immunotherapy for the most common arrhythmia.
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