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Updated: Dec 6, 2025
Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
Published on: May 21, 2018
Macrophage pyroptosis is mediated by immunoproteasome subunit β5i (LMP7) in abdominal aortic aneurysm
Xu Zhang1, Fangda Li1, Wei Wang1
1Vascular Surgery Department, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Abstract:
Macrophages contribute to abdominal aortic aneurysm (AAA), but the effect of macrophage on AAA formation is not totally understood. Recent research proved that macrophage pyroptosis plays an important role in many cardiovascular disease. However, whether macrophage pyroptosis is involved in AAA and its mechanism remains unknown. In this study, we found that the pyroptosis significantly increased in AAA tissues. β5i inhibitor PR-957 treatment or β5i deficiency markedly ameliorated AAA formation and decreased the pyroptosis. Pyroptosis were also significantly attenuated in bone marrow derived macrophages (BMDM) from β5i-/- mice compared with the control group when they were subjected to OXLDL. Mechanistically, β5i may promote activation of NFκB which augment NLRP3 expression. In conclusion, this study suggested macrophages pyroptosis are involved in AAA and inhibition or knockout of β5i decreased macrophage pyroptosis via IκB/NFκB pathway.
Insights
Macrophage pyroptosis is implicated in abdominal aortic aneurysm (AAA) development. Inhibiting or removing β5i reduces pyroptosis, ameliorating AAA formation via the IκB/NFκB pathway.
Area of Science:
- Cardiovascular Research
- Immunology
- Cellular Biology
Background:
- Macrophages are key players in abdominal aortic aneurysm (AAA) pathogenesis.
- Macrophage pyroptosis is increasingly recognized in cardiovascular diseases, but its role in AAA is unclear.
Purpose of the Study:
- To investigate the involvement of macrophage pyroptosis in AAA formation.
- To elucidate the underlying mechanism of macrophage pyroptosis in AAA.
Main Methods:
- Analysis of pyroptosis in human AAA tissues.
- Treatment with a β5i inhibitor (PR-957) or using β5i-deficient mice (β5i-/-).
- Assessment of pyroptosis in bone marrow-derived macrophages (BMDM) stimulated with OXLDL.
Main Results:
- Pyroptosis was significantly elevated in AAA tissues.
- β5i inhibition or deficiency markedly reduced AAA formation and pyroptosis.
- Pyroptosis was attenuated in BMDM from β5i-/- mice.
Conclusions:
- Macrophage pyroptosis is involved in AAA pathogenesis.
- Inhibition or knockout of β5i ameliorates AAA by decreasing macrophage pyroptosis.
- β5i may promote AAA via the IκB/NFκB pathway, augmenting NLRP3 expression.
