A Calixsalan-based ionizable lipid for macrophage-targeted Trem2 siRNA delivery attenuates atherosclerosis - PubMed
5 hours ago
- #Atherosclerosis
- #Macrophage
- #siRNA
- A novel Calixsalan-based ionizable lipid enables macrophage-targeted lipid nanoparticles (LNPs) for siRNA delivery.
- Targeting Trem2 via siRNA attenuates atherosclerosis by silencing macrophage Trem2 and suppressing pro-atherogenic pathways.
- Circulating soluble Trem2 (sTrem2) is identified as an independent clinical predictor of coronary artery disease.
- Macrophages promote vascular smooth muscle cell proliferation and migration via PDGF-BB secretion in a KLF4-dependent manner.
- Intravenous administration of targeted LNPs in mice significantly reduced plaque burden, validating Trem2 silencing as a therapeutic strategy.