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Therapeutic Spp1 silencing in TREM2+ cardiac macrophages suppresses atrial fibrillation.
Momin, Noor; Pabel, Steffen; Rudra, Arnab; Kumowski, Nina; Lee, I-Hsiu; Mentkowski, Kyle; Yamazoe, Masahiro; Stengel, Laura; Muse, Charlotte G; Seung, Hana; Paccalet, Alexandre; Gonzalez-Correa, Cristina; Jacobs, Emily B; Grune, Jana; Schloss, Maximilian J; Sossalla, Samuel; Wojtkiewicz, Gregory; Iwamoto, Yoshiko; McMullen, Patrick; Mitchell, Richard N; Ellinor, Patrick T; Anderson, Daniel G; Naxerova, Kamila; Nahrendorf, Matthias; Hulsmans, Maarten.
Afiliação
  • Momin N; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Pabel S; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Rudra A; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
  • Kumowski N; Center for Precision Engineering for Health, University of Pennsylvania, Philadelphia, PA, USA.
  • Lee IH; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Mentkowski K; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Yamazoe M; Gordon Center for Medical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Stengel L; Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany.
  • Muse CG; Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, USA.
  • Seung H; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Paccalet A; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Gonzalez-Correa C; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Jacobs EB; Harvard-MIT Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Grune J; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Schloss MJ; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Sossalla S; Gordon Center for Medical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Wojtkiewicz G; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Iwamoto Y; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • McMullen P; Gordon Center for Medical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Mitchell RN; Blavatnik Institute, Genetics, Harvard Medical School, Boston, MA, USA.
  • Ellinor PT; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Anderson DG; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Naxerova K; Gordon Center for Medical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Nahrendorf M; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Hulsmans M; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
bioRxiv ; 2024 Aug 10.
Article em En | MEDLINE | ID: mdl-39149373
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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Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: BioRxiv Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: BioRxiv Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos