articleScienceJan 29, 2026Closed access

Targeting modulated vascular smooth muscle cells in atherosclerosis via FAP-directed immunotherapy

JAJunedh AmruteIJIn‐Hyuk JungTYTracy YamawakiWLWen-Ling LinABAndrea Bredemeyer

Amgen (United States) · Washington University in St. Louis · +10 more institutions

PubMed
Indexed incrossrefpubmed

Abstract

Vascular smooth muscle cell (VSMC) diversification drives atherosclerotic coronary artery disease (CAD), but the mechanisms governing these cell state transitions remain unclear. We applied multiomic single-cell profiling, epitope mapping, and spatial transcriptomics across 27 human coronary arteries, identifying fibroblast activation protein (FAP) as a marker of modulated VSMCs. Lineage tracing in mice indicated that FAP + cells originate from Myh11 + VSMCs, and FAP positron emission tomography imaging in CAD patients showed plaque uptake. FAP + cell states resided in the macrophage-rich neo-intima. Therapeutically, we developed an anti-FAP bispecific T cell engager, which reduced plaque burden and remodeled…

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Authors

39

Topics & keywords

Topics
Keywords
  • Vascular smooth muscle
  • Immunotherapy
  • Coronary artery disease
  • Cell
  • Smooth muscle
  • Epitope
  • Transcriptome
  • Artery
UN Sustainable Development Goals
  • Good health and well-being
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