Phenotypic plasticity of smooth muscle cells (SMCs) and endothelial cells (ECs) contributes to atherosclerotic plaque composition and stability, yet how shifts in one population influence the contribu Show more
Phenotypic plasticity of smooth muscle cells (SMCs) and endothelial cells (ECs) contributes to atherosclerotic plaque composition and stability, yet how shifts in one population influence the contribution and function of the other under conditions of vascular stress, such as irradiation, is poorly understood. A major limitation has been the inability to We generated dual lineage-tracing Dual lineage tracing specifically and simultaneously labeled SMC- and EC-derived cells in healthy and atherosclerotic vessels. Irradiation induced divergent responses: SMC-derived cells failed to invest in lesions and upregulated stress-activated inflammatory genes, whereas EC-derived cells expanded and upregulated SMC-associated genes. However, EC-derived cells within lesions failed to induce extracellular matrix genes, and lesions from irradiated mice exhibited reduced collagen content and fewer ACTA2 Dual lineage-tracing of SMCs and ECs demonstrated that irradiation-induced loss of lesional SMC and expansion of EC-derived ACTA2 Show less