Aortic & peripheral vascular disease
LXRα Promotes Abdominal Aortic Aneurysm Formation Through UHRF1 Epigenetic Modification of miR-26b-3p
Authors' conclusion
Our study reveals a pivotal role of the LXRα/UHRF1/miR-26b-3p axis in AAA
Study context
- Population
- Human abdominal aortic aneurysm (AAA) aortas and mouse AAA models (angiotensin II or calcium chloride (CaCl2))
- Comparison
- Nr1h3 knockout vs wild-type in murine AAA models
Methodological detailsglobal and VSMC-specific Nr1h3-knockout mice, angiotensin II and CaCl2 AAA mouse models
- Global and VSMC-specific Nr1h3-knockout mice
- Angiotensin II and CaCl2 AAA mouse models
Main finding
As reported in the abstract
- LXRα upregulated in aortas of patients with AAA and in angiotensin II- or CaCl2-treated mice
- Global or VSMC-specific Nr1h3 knockout inhibited AAA formation in 2 mouse models
- Loss of LXRα prevented extracellular matrix degeneration, inflammation and VSMC phenotypic switching
- Uhrf1 identified as a direct target gene of LXRα; UHRF1 enhanced susceptibility to AAA in both models
- UHRF1 recruitment to miR-26b promoter led to DNA hypermethylation, closed chromatin and miR-26b downregulation in AAA
- Underexpression of miR-26b-3p correlated with high risk in patients with AAA
- Maintaining miR-26b-3p expression prevented AAA progression
Original publication
LXRα Promotes Abdominal Aortic Aneurysm Formation Through UHRF1 Epigenetic Modification of miR-26b-3p. Circulation. Published 1 April 2024. doi:10.
Summarised from the published abstract; every number is checked against it