Aortic & peripheral vascular disease
Carbonylation of Runx2 at K176 by 4-Hydroxynonenal Accelerates Vascular Calcification
Authors' conclusion
Our results suggest that 4-HNE increases Runx2 stabilization by directly carbonylating its K176 site and promotes vascular calcification.
Study context
- Population
- Patients with CKD and controls; donor coronary plaques; patients with CAD undergoing coronary CT angiography; ALDH2 knockout, smooth muscle cell-specific knockout and transgenic mice; mouse and human aortic smooth muscle cellsCAD patients, rs671 analysis
- Participants
- 658 patients
Main finding
As reported in the abstract
- Elevated 4-HNE levels in serum of CKD patients and model mice, and in calcified artery sections
- ALDH2 knockout or smooth muscle cell-specific ALDH2 knockout accelerated vascular calcification in mice; overexpression or activation prevented it
- CAD patients with ALDH2 rs671 mutation developed more severe coronary calcification
- 4-HNE promoted calcification and osteochondrogenic differentiation of mouse and human aortic smooth muscle cells in vitro
- 4-HNE increased Runx2; its pro-calcification effect was ablated by Runx2 knockdown
- Mutation of Runx2 at K176 reduced its carbonylation and eliminated 4-HNE-induced Runx2 upregulation
Original publication
Carbonylation of Runx2 at K176 by 4-Hydroxynonenal Accelerates Vascular Calcification. Circulation. Published 13 February 2024. doi:10.
Summarised from the published abstract; every number is checked against it