Therapeutic Spp1 silencing in TREM2 + cardiac macrophages suppresses atrial fibrillation.
Noor MominSteffen PabelArnab RudraNina KumowskiI-Hsiu LeeKyle MentkowskiMasahiro YamazoeLaura StengelCharlotte G MuseHana SeungAlexandre PaccaletCristina Gonzalez-CorreaEmily B JacobsJana GruneMaximilian J SchlossSamuel SossallaGregory WojtkiewiczYoshiko IwamotoPatrick McMullenRichard N MitchellPatrick T EllinorDaniel G AndersonKamila NaxerovaMatthias NahrendorfMaarten HulsmansPublished in: bioRxiv : the preprint server for biology (2024)
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.
Keyphrases
- atrial fibrillation
- catheter ablation
- left atrial
- oral anticoagulants
- left atrial appendage
- left ventricular
- direct oral anticoagulants
- signaling pathway
- heart failure
- cancer therapy
- percutaneous coronary intervention
- liver fibrosis
- coronary artery disease
- single cell
- risk factors
- insulin resistance
- drug delivery
- adipose tissue
- venous thromboembolism
- skeletal muscle
- hyaluronic acid