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Updated: Jan 31, 2026

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
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.
None:
Vascular smooth muscle cell (VSMC) diversification drives atherosclerotic coronary artery disease (CAD). 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 PET imaging in CAD patients showed plaque uptake. FAP+ cells states resided in the macrophage-rich neo-intima. Therapeutically, we developed an anti-FAP bispecific T-cell engager, which reduced plaque burden and remodeled the stromal-immune microenvironment through T-cell clonal expansion. Our study delivers a single-cell and spatial atlas of human CAD, establishes FAP as a marker of modulated VSMCs, and highlights immunotherapy for lipid-independent targets.
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