HEG1 Protects Against Atherosclerosis by Regulating Stable Flow-Induced KLF2/4 Expression in Endothelial Cells
Authors' conclusion
Our findings indicate that HEG1 is a novel mediator of atheroprotective endothelial responses to flow and a potential therapeutic target.
Study context
- Population
- Mouse arteries, human aortic endothelial cells (HAECs) and human coronary arteries; hypercholesterolemic mice (AAV-PCSK9 + Western diet)
- Comparison
- HEG1iECKO vs littermate-control mice; HEG1 knockdown in HAECs
Methodological detailssingle-cell RNA-sequencing reanalysis, endothelial-targeted, tamoxifen-inducible HEG1 knockout mice, siRNA knockdown in HAECs, partial carotid ligation model
- Single-cell RNA-sequencing reanalysis
- Endothelial-targeted, tamoxifen-inducible HEG1 knockout mice
- siRNA knockdown in HAECs
- Partial carotid ligation model
Main finding
As reported in the abstract
- S-flow induced HEG1 expression at mRNA and protein levels in vivo and in vitro
- HEG1 knockdown prevented s-flow-induced endothelial responses, incl. monocyte adhesion, permeability and migration
- HEG1 knockdown prevented s-flow-induced KLF2/4 expression via KRIT1 and the MEKK3-MEK5-ERK5-MEF2 pathway in HAECs
- HEG1iECKO vs littermate controls (2 weeks hypercholesterolemia + partial carotid ligation): advanced plaques with increased necrotic core area, thin-capped fibroatheroma, inflammation and intraplaque hemorrhage
- Western diet 2 months: exacerbated atherosclerosis in the arterial tree in both sexes and in the aortic sinus in males but not females
- Endothelial HEG1 expression reduced in human coronary arteries with advanced atherosclerotic plaques
Original publication
HEG1 Protects Against Atherosclerosis by Regulating Stable Flow-Induced KLF2/4 Expression in Endothelial Cells. Circulation. Published 15 December 2023. doi:10.
Summarised from the published abstract; every number is checked against it