A rare pre-existing progenitor-like Primed SMC compartment is the dominant inferred source of SMC-derived cellularity in vascular injury and atherosclerosis

A rare progenitor-like Primed SMC compartment present before lesion formation in sham-operated mouse carotid arteries and across Myh11-lineage datasets is the dominant inferred source of SMC-derived lesional cellularity.

• Why it matters: The role of pre-existing SMC states in vascular lesions is unresolved, limiting understanding of whether lesions arise mainly from phenotypic switching or from expansion of resident SMC programs.
• What they did: The study identified Primed SMCs in sham carotid arteries and Myh11-lineage marked mouse aortic datasets, and found a Primed-like counterpart in non-diseased human aorta, using mapping and cross-dataset trajectory/graph analyses.
• The result: After carotid ligation and during high-fat diet-induced atherosclerosis in Ldlr-/- and Apoe-/- mice, disease-associated Primed, cycling, and fibrochondrocyte populations preferentially map to baseline Primed SMCs while contractile SMCs are depleted as inferred feeder sources.