Year: 2026
Type: article
Abstract: Rupture of unstable atherosclerotic plaques is a major cause of mortality. Endothelial-to-mesenchymal transition associates with advanced atherosclerotic plaques and contributes to plaque progression. We examined the role of Twist1 , a transcription factor that drives endothelial-to-mesenchymal transition, in plaque progression by inducible deletion from endothelial cells in hypercholesterolemic mice ( Twist1 ECKO Apo -/- ). Single-cell RNA sequencing coupled to endothelial cell-tracking reveals that Twist1 promotes endothelial-to-mesenchymal transition in advanced atherosclerotic plaques. Histological analyses demonstrate that endothelial Twist1 promotes plaque growth and hallmarks of plaque stability (collagen, ACTA2-positive cells) and reduces features of instability (necrosis, macrophage accumulation). Analysis of cultured human aortic endothelial cells shows that TWIST1 contributes to endothelial-to-mesenchymal transition by promoting migration and proliferation through the transcriptional coactivator PELP1. Additionally, TWIST1 promotes endothelial cell proliferation via AEBP1-dependent upregulation of COL4A1. These findings challenge the prevailing view that endothelial-to-mesenchymal transition uniquely destabilizes plaques, by suggesting that TWIST1-driven endothelial-to-mesenchymal transition can promote plaque stability, offering new insights into atherosclerosis pathophysiology and therapeutic potential.
Source: Nature Communications
Authors: Blanca Tardajos Ayllon, Mannekomba Diagbouga, Ankita Das, Siyu Tian, Andreas Edsfeldt, Joanna Kalucka, Jovana Serbanovic-Canic, Emily Chambers, Jiangming Sun, Chrysostomi Gialeli, Mark Dunning, Sheila E. Francis, Xiuying Li, Akiko Mammoto, Michael Simons, Helle F. Jørgensen, Isabel Goncalves, Suowen Xu, Paul C. Evans
Institutions: Queen Mary University of London, William Harvey Research Institute, Lund University, Skåne University Hospital, Aarhus University, Aarhus University Hospital, Steno Diabetes Center Aarhus, Insigneo, University of Sheffield, Southwest Medical University, Affiliated Hospital of Southwest Medical University, Medical College of Wisconsin, Yale University, University of Cambridge, University of Science and Technology of China
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: British Heart Foundation, Fondation Leducq, Stiftelsen för Strategisk Forskning, National Natural Science Foundation of China, Lunds Universitet, Svenska Sällskapet för Medicinsk Forskning, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, STROKE-Riksförbundet, National Institutes of Health
Awards: G1590297379, G2004031785, G263730981, G3918735012, G5662997369, The vulnerable atherosclerotic plaque: mechanisms of development and tools for its identification, G5948802825, G6558030351, G67379338, LUDC-IRC för individanpassad medicin i diabetes, Role of the transcription factor twist1 in endothelial pathophysiology and atherosclerosis progression (renewal), Apoptosis and efferocytosis as mechanisms of impaired fibrotic tissue repair in diabetes associated vascular complications, G894361248, G9000154909
OpenAlex ID: W7130337679