Targeting endothelial to mesenchymal transition in atherosclerosis

High glucose/high lipid stress in endothelial cells and ApoE−/− atherosclerotic settings induces histone lactylation (H3K18la) at the SULF1 locus, leading to SULF-1 upregulation. Elevated SULF-1 activates a downstream HMOX1–WNT5A/WNT5B–SLUG signalling axis, driving endothelial-to-mesenchymal transition (EndMT). EndMT contributes to reduced endothelial viability, enhanced oxidative stress with iron overload, lipid peroxidation, and plaque instability, thereby promoting atherosclerotic progression. Created in BioRender. Sachse, M. (2026) https://BioRender.com/ky15cio.