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EZH2 inhibition via GSK-126 mitigates EndMT and atherosclerosis in diabetes: A translational epigenetic approach.

GSE316326 Homo sapiens Expression profiling by high throughput sequencing 7 samples Submitted 2026/06/03 Platform GPL24676
Summary
Atherosclerosis drives cardiovascular morbidity in diabetes, with endothelial-to-mesenchymal transition (EndMT) as a key contributor. While 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 trimethylation is elevated in carotid plaques from diabetic patients and in 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/TNF-α or serum from coronary artery disease patients, EZH2 blockade via GSK-126 or shRNA 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.
Published in
EZH2 inhibition via GSK-126 mitigates EndMT and atherosclerosis in diabetes: A translational epigenetic approach
Aziz M, Sourris KC, Pinzon-Cortes JA et al. · Science advances 2026 · PMID 42213823 · doi:10.1126/sciadv.aee5560
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Also filed as BioProject PRJNA1402321 and SRA study SRP661858. Searching any of these in the dataset finder brings you back here.

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