Longevity & AgingSenescent Vascular Cells Mapped in Atherosclerosis Using Single-Cell and Spatial Transcriptomics
Using single-cell RNA sequencing of whole aortas from atherosclerotic mice, researchers identified four distinct clusters of vascular smooth muscle cells, fibroblasts, and T cells enriched for senescence features. These clusters expanded under high-fat diet conditions and were reduced by treatment with the senolytic drug ABT-737. A core senescence signature—including Spp1, Ctsb, and Tnfrsf11b mRNAs—was derived and validated using spatial transcriptomics in a second mouse model and in human vascular smooth muscle cell cultures. ABT-737 treatment improved plaque stability, reduced necrotic core area, increased fibrous cap thickness, and lowered vascular stiffness, suggesting that clearing senescent cells promotes beneficial arterial remodeling without necessarily reducing plaque size.
