Related Experiment Video

Updated: Jan 31, 2026

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
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Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation

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

Junedh M Amrute1,2,3,4,5, In-Hyuk Jung1,5, Tracy Yamawaki2

  • 1Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA.

Science (New York, N.Y.)
|January 29, 2026
PubMed

Insights

Fibroblast activation protein (FAP) marks changing vascular smooth muscle cells in coronary artery disease (CAD). Targeting FAP with immunotherapy offers a new treatment strategy for CAD.

Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Translational Medicine

Background:

  • Vascular smooth muscle cell (VSMC) diversification is a key driver of atherosclerotic coronary artery disease (CAD).
  • The precise mechanisms controlling VSMC state transitions in CAD remain largely unknown.
  • Understanding these cellular dynamics is crucial for developing effective CAD therapies.

Purpose of the Study:

  • To elucidate the cellular mechanisms underlying VSMC diversification in human CAD.
  • To identify novel cellular markers and therapeutic targets for atherosclerotic disease.
  • To evaluate the potential of targeting identified markers for CAD immunotherapy.

Main Methods:

  • Multiomic single-cell profiling and spatial transcriptomics were performed on 27 human coronary arteries.
  • Epitope mapping and lineage tracing in mouse models were utilized.
  • Positron emission tomography (PET) imaging with FAP tracers was conducted in CAD patients.
  • Development and testing of an anti-FAP bispecific T-cell engager therapy.

Main Results:

  • Fibroblast activation protein (FAP) was identified as a marker for modulated VSMCs in human CAD.
  • FAP-expressing cells were found to originate from Myh11+ VSMCs and reside in the macrophage-rich neo-intima.
  • FAP PET imaging demonstrated significant plaque uptake in CAD patients.
  • Therapeutic intervention with an anti-FAP bispecific T-cell engager reduced atherosclerotic plaque burden and modulated the stromal-immune microenvironment.

Conclusions:

  • This study provides a comprehensive single-cell and spatial atlas of human CAD, revealing key cellular players.
  • FAP is established as a reliable marker for VSMC modulation in the context of atherosclerosis.
  • Targeting FAP via immunotherapy presents a promising lipid-independent therapeutic strategy for CAD.

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