EZH2 inhibition via GSK-126 mitigates EndMT and atherosclerosis in diabetes: A translational epigenetic approach.
M, A., KC, S., JA, P.C., TJ, B., A, D., S, M., J, O., AC, C., ME, C., & KAM, J.D. (2026). EZH2 inhibition via GSK-126 mitigates EndMT and atherosclerosis in diabetes: A translational epigenetic approach.. Science advances. https://doi.org/10.1126/sciadv.aee5560
M A, KC S, JA PC, TJ B, A D, S M, et al. EZH2 inhibition via GSK-126 mitigates EndMT and atherosclerosis in diabetes: A translational epigenetic approach.. Science advances. 2026; doi: 10.1126/sciadv.aee5560
M A, KC S, JA PC, et al. EZH2 inhibition via GSK-126 mitigates EndMT and atherosclerosis in diabetes: A translational epigenetic approach.[J]. Science advances. 2026. DOI: 10.1126/sciadv.aee5560.
@article{m2026,
author = {Aziz M and Sourris KC and Pinzon-Cortes JA and Block TJ and Dai A and Maxwell S and Okabe J and Calkin AC and Cooper ME and Jandeleit-Dahm KAM},
title = {EZH2 inhibition via GSK-126 mitigates EndMT and atherosclerosis in diabetes: A translational epigenetic approach.},
journal = {Science advances},
year = {2026},
doi = {10.1126/sciadv.aee5560},
note = {PMID: 42213823},
}
TY - JOUR AU - Aziz M AU - Sourris KC AU - Pinzon-Cortes JA AU - Block TJ AU - Dai A AU - Maxwell S AU - Okabe J AU - Calkin AC AU - Cooper ME AU - Jandeleit-Dahm KAM TI - EZH2 inhibition via GSK-126 mitigates EndMT and atherosclerosis in diabetes: A translational epigenetic approach. T2 - Science advances PY - 2026 DO - 10.1126/sciadv.aee5560 AN - PMID:42213823 ER -
Atherosclerosis drives cardiovascular morbidity in diabetes, with endothelial-to-mesenchymal transition (EndMT) as a key contributor. Whereas epigenetic regulators are increasingly implicated in atherosclerotic progression, the specific role of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, in EndMT in diabetes-associated atherosclerosis remains unclear. We show that EZH2-mediated H3K27 (histone H3 at lysine-27) trimethylation is elevated in carotid plaques from patients with diabetes and in the aortic endothelium of diabetic Apoe-/- mice. Pharmacologic EZH2 inhibition with GSK-126 attenuated EndMT and reduced atherosclerotic burden in diabetic mice. In human aortic endothelial cells exposed to high glucose/tumor necrosis factor-α or serum from patients with coronary artery disease, EZH2 blockade via GSK-126 or short hairpin RNA suppressed EndMT and reversed transcriptional programs assessed by RNA sequencing, including COL4A1 and NR2F2. These findings identify EZH2 as a driver of EndMT in diabetes-associated atherosclerosis and highlight EZH2 inhibition as a potential therapeutic strategy to limit vascular pathology.