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Updated: May 12, 2025
Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice
Published on: February 20, 2019
Clusterin ameliorates diabetic atherosclerosis by suppressing macrophage pyroptosis and activation
Lingling Xuan1, Lulu Ren1, Xiaoxu Kang2
1Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Insights
Clusterin (CLU) protects against diabetic atherosclerosis by reducing inflammation and macrophage pyroptosis. CLU shows potential as a therapeutic target for this condition.
Area of Science:
- Cardiovascular Biology
- Immunology
- Metabolic Diseases
Background:
- Clusterin (CLU) is a known protective protein in various diseases.
- The specific role of CLU in diabetic atherosclerosis remains unclear.
- Understanding CLU's function is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the role of clusterin (CLU) in diabetic atherosclerosis.
- To elucidate the underlying molecular mechanisms of CLU's action.
- To assess CLU's potential as a therapeutic target.
Main Methods:
- Utilized Clu knockout and overexpressed murine models for in vivo studies.
- Assessed atherosclerotic plaque formation using H&E and Oil Red O staining.
- Quantified inflammatory markers (TNF-α, IL-6, IL-1β) and macrophage infiltration (F4/80, CD68) via immunohistochemistry, Western blot, qPCR, and ELISA.
- Examined macrophage pyroptosis using transmission electron microscopy.
Main Results:
- CLU overexpression reduced atherosclerotic plaque formation and macrophage infiltration in mice.
- Clu knockout exacerbated plaque development and inflammatory responses.
- CLU inhibited the release of TNF-α, IL-6, and IL-1β in macrophages.
- CLU suppressed inflammatory factor release and macrophage pyroptosis in diabetic atherosclerosis models.
Conclusions:
- Clusterin (CLU) ameliorates diabetic atherosclerosis by suppressing macrophage pyroptosis and inflammatory factor release.
- CLU demonstrates significant potential as a therapeutic target for diabetic atherosclerosis.
- Further research into CLU-based therapies is warranted.
Background:
It has been demonstrated that clusterin (CLU) is a protective protein involved in a variety of diseases and disorders. However, the role of CLU in diabetic atherosclerosis is not elucidative. The objective of this study is to investigate the role of CLU in diabetic atherosclerosis and the molecular mechanisms.
Method:
In in vivo experiments, Clu knockout and overexpressed murine models were used to investigate the role of Clu in diabetic atherosclerosis. Atherosclerotic plaque formation was determined by hematoxylin-eosin (H&E) staining and Oil Red O staining. F4/80 and CD68 levels were determined by immunohistochemical staining. Transmission electron microscopy was used to observe changes in cell pyroptosis morphology. NLRP3 and IL-1β levels were determined by Western blot and immunofluorescence staining. In in vitro experiments, TNF-α, IL-6, and IL-1β levels in THP-1 derived macrophages were determined by real-time qPCR and ELISA.
Results:
We found that Clu-overexpression reduced while Clu knockout promoted atherosclerotic plaque formation, macrophage infiltration and inflammatory factor expression in mouse aortic plaques. Consistently, CLU overexpression inhibits the production of TNF-α, IL-6, and IL-1β in THP-1 derived macrophages. Moreover, Clu inhibited the release of inflammatory factors and macrophage pyroptosis in diabetic atherosclerosis murine models.
Conclusion:
Our study revealed that CLU could ameliorate diabetic atherosclerosis via suppressing inflammatory factors release and pyroptosis of macrophage. CLU may be a promising therapeutic target for diabetic atherosclerosis.
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