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Updated: Mar 7, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Dickkopf-3 Ablation Attenuates the Development of Atherosclerosis in ApoE-Deficient Mice
Wen-Lin Cheng1,2,3, Yang Yang1,4, Xiao-Jing Zhang1,2,3
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Background:
Dickkopf-3 (DKK3) is a negative regulator of the Wnt/β-catenin signaling pathway, which is involved in inflammation. However, little is known about the relationship between DKK3 expression and the progression of atherosclerosis. The aim of the present study was to define the role of DKK3 and its potential mechanism in the development of atherosclerosis.
Methods And Results:
Immunofluorescence analysis showed that DKK3 was strongly expressed in macrophages of atherosclerotic plaques from patients with coronary heart disease and in hyperlipidemic mice. The expression level was significantly increased in atherogenesis. DKK3-/-ApoE-/- mice exhibited a significant decrease in atherosclerotic lesions in the entire aorta, aortic sinus, and brachiocephalic arteries. Transplantation of bone marrow from DKK3-/-ApoE-/- mice into lethally irradiated ApoE-/- recipients resulted in a reduction of atherosclerotic lesions, compared with the lesions in recipients transplanted with ApoE-/- donor cells, suggesting that the effect of DKK3 deficiency was largely mediated by bone marrow-derived cells. A reduction in the necrotic core size, accompanied by increased collagen content and smooth muscle cells and decreased accumulation of macrophages and lipids, contributed to the stability of plaques in DKK3-/-ApoE-/- mice. Furthermore, multiple proinflammatory cytokines exhibited marked decreases in DKK3-/-ApoE-/- mice. Finally, we observed that DKK3 ablation increased β-catenin expression in the nuclei of macrophages both in vivo and in vitro.
Conclusions:
DKK3 expression in macrophages is involved in the pathogenesis of atherosclerosis through modulation of inflammation and inactivation of the Wnt/β-catenin pathway.
Insights
Dickkopf-3 (DKK3) protein promotes atherosclerosis by increasing inflammation. Removing DKK3 stabilizes plaques and reduces disease progression, highlighting its role in cardiovascular health.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Immunology
Background:
- Dickkopf-3 (DKK3) negatively regulates the Wnt/β-catenin pathway, implicated in inflammation.
- The role of DKK3 in atherosclerosis development remains largely undefined.
Purpose of the Study:
- To investigate the role of DKK3 in atherosclerosis.
- To elucidate the underlying mechanisms of DKK3's involvement in atherosclerosis.
Main Methods:
- Immunofluorescence analysis of DKK3 expression in human and mouse atherosclerotic plaques.
- Assessment of atherosclerosis in DKK3 knockout and ApoE knockout mice.
- Bone marrow transplantation studies.
- Analysis of plaque composition and inflammatory markers.
Main Results:
- DKK3 expression is elevated in macrophages within atherosclerotic plaques.
- DKK3 deficiency significantly reduces atherosclerotic lesion size and promotes plaque stability.
- DKK3 ablation decreases pro-inflammatory cytokines and macrophage accumulation.
- DKK3 deficiency leads to increased nuclear β-catenin in macrophages.
Conclusions:
- DKK3 expression in macrophages contributes to atherosclerosis pathogenesis.
- DKK3 modulates inflammation and inactivates the Wnt/β-catenin pathway in atherosclerosis.
- Targeting DKK3 may offer a therapeutic strategy for atherosclerosis.
