Perivascular adipose single-cell atlas identifies CD55+ adipose-derived stem cells as vascular remodeling regulators in atherosclerosis

Atherosclerotic carotid stenosis is a major cause of stroke, yet the mechanisms driving plaque instability remain incompletely understood. Perivascular adipose tissue (PVAT), the fat surrounding blood vessels, has been implicated in advanced atherosclerosis progression, but its cellular contributions are largely unknown. Here we show that PVAT contains two distinct adipose-derived stem cell (ADSC, multipotent progenitor cells within fat tissue) subsets. By analyzing 169 clinical samples using single-cell RNA sequencing and flow cytometry and pathological staining, we identify CD55⁺ADSCs as elevated in patients with symptomatic carotid stenosis or prior stroke. These cells migrate into plaques, differentiate into endothelial cells and promote pathological angiogenesis and vascular remodeling through FGF2 secretion thereby destabilising plaques. A second population, CXCL14+ADSCs exacerbate inflammation by recruiting immune cells via the CXCL12-CXCR4 axis. Our findings identify perivascular CD55+ADSCs as a therapeutic target for atherosclerosis management. Atherosclerotic carotid stenosis leads to stroke, but how perivascular adipose tissue (PVAT) drives plaque instability is poorly understood. Here the authors show that PVAT harbours distinct ADSC subsets, with CD55⁺ADSCs promoting plaque angiogenesis via FGF2 and CXCL14⁺ADSCs enhancing inflammation, driving plaque destabilization.