A rare pre-existing progenitor-like Primed SMC compartment is the dominant inferred source of SMC-derived cellularity in vascular injury and atherosclerosis
- 1Dublin City University
Abstract
The contribution of pre-existing smooth muscle cell (SMC) states to vascular lesions remains unresolved. Here we identify a rare, progenitor-like Primed SMC compartment before lesion formation in sham-operated carotid arteries and across Myh11-lineage marked mouse aortic datasets, with a Primed-like counterpart in non-diseased human aorta. Primed SMCs retain SMC identity while combining attenuated contractile programmes with conserved niche-associated (Cd34, Fst, Tnfrsf11b) and matricellular (Vcam1, Thbs1, Timp1) cores, overlaid by vessel-specific developmental signatures (Nrn1, Gdf10, Scx). 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, whereas contractile SMCs are depleted as inferred feeder sources. Concordant trajectory, graph-based and cross-dataset analyses support a model in which this pre-existing compartment is the dominant inferred source of SMC-derived lesional cellularity. These findings favour expansion and diversification of the Primed compartment over widespread phenotypic switching of contractile SMCs.
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BibTeX
@misc{wani2026rare,
title = {{A rare pre-existing progenitor-like Primed SMC compartment is the dominant inferred source of SMC-derived cellularity in vascular injury and atherosclerosis}},
author = {S. Wani and M. Kitching and S. Aboulhassanzadeh and T.-S. Lungu and I. Kilicgun and K. Ulibarri and W. Liu and A. Floudas and E. M. Redmond and P. A. Cahill},
howpublished = {bioRxiv},
year = {2026},
month = jun,
doi = {10.64898/2026.06.28.735042},
url = {https://www.biorxiv.org/content/10.64898/2026.06.28.735042v7},
note = {CC BY},
}
RIS
TY - UNPB
TI - A rare pre-existing progenitor-like Primed SMC compartment is the dominant inferred source of SMC-derived cellularity in vascular injury and atherosclerosis
AU - S. Wani
AU - M. Kitching
AU - S. Aboulhassanzadeh
AU - T.-S. Lungu
AU - I. Kilicgun
AU - K. Ulibarri
AU - W. Liu
AU - A. Floudas
AU - E. M. Redmond
AU - P. A. Cahill
PY - 2026
DA - 2026/06/28
PB - bioRxiv
DO - 10.64898/2026.06.28.735042
UR - https://www.biorxiv.org/content/10.64898/2026.06.28.735042v7
AB - The contribution of pre-existing smooth muscle cell (SMC) states to vascular lesions remains unresolved. Here we identify a rare, progenitor-like Primed SMC compartment before lesion formation in sham-operated carotid arteries and across Myh11-lineage marked mouse aortic datasets, with a Primed-like counterpart in non-diseased human aorta. Primed SMCs retain SMC identity while combining attenuated contractile programmes with conserved niche-associated (Cd34, Fst, Tnfrsf11b) and matricellular (Vcam1, Thbs1, Timp1) cores, overlaid by vessel-specific developmental signatures (Nrn1, Gdf10, Scx). 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, whereas contractile SMCs are depleted as inferred feeder sources. Concordant trajectory, graph-based and cross-dataset analyses support a model in which this pre-existing compartment is the dominant inferred source of SMC-derived lesional cellularity. These findings favour expansion and diversification of the Primed compartment over widespread phenotypic switching of contractile SMCs.
ER -