Related Experiment Video
Updated: Jun 28, 2025
08:43
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
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Orphan Nuclear Receptor NR4A3 Promotes Vascular Calcification via Histone Lactylation
Wenqi Ma1,2, Kangni Jia1,2, Haomai Cheng1,2
1Department of Cardiovascular Medicine, Ruijin Hospital (W.M., K.J., H.C., Z.L., H.Z., H.X., L.Z., Z.W., Y.C., H.S., L.Y., Z.C., L.L., R.Z., X.Y.), Shanghai Jiao Tong University School of Medicine, China.
Circulation Research
|April 17, 2024
Summary
Nuclear receptor subfamily 4 group A member 3 (NR4A3) drives medial arterial calcification by enhancing glycolysis and histone lactylation. NR4A3 deficiency reduces vascular calcification, offering a potential therapeutic target.
Area of Science:
- Vascular Biology
- Epigenetics
- Metabolism
Background:
- Medial arterial calcification is a chronic vascular disorder distinct from atherosclerosis.
- It is prevalent in chronic kidney disease, diabetes, and aging.
- The role of NR4A3 in vascular calcification was previously unknown.
Purpose of the Study:
- To investigate the role of NR4A3 in medial arterial calcification.
- To elucidate the molecular mechanisms underlying NR4A3's function in vascular calcification.
Main Methods:
- Generated NR4A3 knockout mice and utilized two medial arterial calcification models.
- Performed RNA-seq and CUT&Tag analysis on NR4A3-deficient vascular smooth muscle cells.
- Investigated NR4A3's regulation of glycolysis and histone lactylation.
Main Results:
- NR4A3 expression is upregulated in calcified arteries.
- NR4A3 deficiency preserved smooth muscle cell phenotype, reduced osteogenic differentiation, and decreased calcium deposition.
- NR4A3 promotes calcification by enhancing glycolysis (ALDOA, PFKL) and histone lactylation, impacting Phospho1 expression.
Conclusions:
- NR4A3-mediated histone lactylation represents a novel metabolome-epigenome signaling pathway in medial arterial calcification.
- Targeting NR4A3 or its downstream pathways may offer therapeutic strategies for vascular calcification.
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