Authors
Steven R Botts, Corey A Scipione, Kristen Schulz, Leandro C D Breda, Kai Ellis, Christy Ho, Sneha Raju, Kamalben Prajapati, Kai Yu, Aniqa B Khan, Chanele K Polenz, Stylianos Z Prattas, Sharon J Hyduk, Christian Cao, Joshua D Wythe, Clint S Robbins, Clint L Miller, Myron I Cybulsky, Jason E Fish, Kathryn L Howe
Published in
Nature communications. Jul 13, 2026. Epub Jul 13, 2026.
Abstract
Endothelial function is a safeguard against atherosclerosis, yet endothelial‑to‑mesenchymal transition (EndMT) can occur at atheroprone sites. How endothelial identity loss contributes to atherogenesis remains unclear. Here we investigated the role of the ETS transcription factor ERG, a key regulator of endothelial identity, in atheroprogression. Inducible endothelial Erg deletion increased plaque burden in hypercholesterolemic mice. Lineage tracing and single‑cell transcriptomics showed that ERG loss drove endothelial dedifferentiation, mesenchymal fate acquisition, and migration and expansion of EndMT cells within plaques, which interacted with pro‑atherogenic cells. ERG loss also caused early disruption of barrier function, promoting lipid uptake and foam cell accumulation in normally atheroresistant regions. In human atherosclerotic plaques, ERG chromatin accessibility and expression were reduced, with transcriptional changes mirroring those in mice. Restoring ERG in cultured EndMT cells reversed mesenchymal programs and re‑established endothelial identity. These findings identify ERG as an enforcer of endothelial function that restricts EndMT to limit atherosclerosis.
PMID:
42443196
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.
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