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Axin2 depletion in macrophages alleviated senescence and increased immune response after myocardial infarction
Yue Zheng1,2,3,4,5,6, Yuchao Wang1,2,3,4,5,6, Bingcai Qi7,4,5,6
1School of Medicine, Nankai University, Tianjin, 300071, China.
Objective And Design:
This study aimed to investigate Axin2 effects on myocardial infarction (MI) using a macrophage Axin2 conditional knockout (cKO) mouse model, RAW264.7 cell line, and human subepicardial tissues from patients with coronary artery bypass graft (CABG).
Material Or Subjects:
Axin2 cKO mice showed decreased cardiac function, reduced edema, increased lymphangiogenesis, and improved repair in MI Few studies border zones. Hypoxic macrophages with Axin2 depletion exhibited decreased senescence, elevated IL6 expression, and increased LYVE1 transcription. Senescent macrophages decreased in patients with CABG and low Axin2 expression.
Treatment:
Treatment options included in this study were MI induction in Axin2 cKO mice, in vitro experiments with RAW264.7 cells, and analysis of human subepicardial tissues.
Methods:
Assays included MI induction, in vitro experiments, and tissue analysis with statistical tests applied.
Results:
Axin2 cKO improved cardiac function, reduced edema, enhanced lymphangiogenesis, and decreased senescence. Hypoxic macrophages with Axin2 depletion showed reduced senescence, increased IL6 expression, and elevated LYVE1 transcription. Senescent macrophages decreased in patients with CABG and low Axin2 expression.
Conclusion:
Targeting Axin2 emerges as a novel therapeutic strategy for regulating cardiac lymphatics and mitigating cell senescence post-MI, evidenced by improved outcomes in Axin2-deficient conditions.
Insights
Targeting Axin2 in macrophages improves cardiac repair after myocardial infarction (MI). Depleting Axin2 reduces cell senescence and enhances lymphatic vessel formation, offering a new therapeutic approach for heart disease.
Area of Science:
- Biomedical research
- Cardiovascular science
- Cell biology
Background:
- Myocardial infarction (MI) remains a leading cause of mortality, with limited therapeutic options for cardiac repair.
- Macrophage-mediated inflammation and senescence play critical roles in post-MI cardiac dysfunction.
- The role of Axin2 in regulating macrophage function and cardiac healing after MI is not well understood.
Discussion:
- Axin2 deficiency in macrophages promotes cardiac repair post-MI by enhancing lymphangiogenesis and reducing interstitial edema.
- In vitro studies demonstrate that Axin2 depletion in hypoxic macrophages reduces cellular senescence and modulates inflammatory signaling (IL6).
- Reduced senescent macrophages were observed in human tissues from patients with coronary artery bypass graft (CABG) and lower Axin2 expression.
Key Insights:
- Conditional knockout of Axin2 in macrophages significantly improves cardiac function and repair following MI.
- Axin2 depletion in macrophages leads to reduced cellular senescence and increased IL6 expression under hypoxic conditions.
- Axin2 plays a crucial role in regulating macrophage senescence and lymphatic vessel development in the context of cardiac injury.
Outlook:
- Targeting Axin2 presents a promising therapeutic strategy for mitigating cell senescence and promoting cardiac lymphatic regeneration post-MI.
- Further research into Axin2-mediated pathways could uncover novel interventions for cardiovascular diseases.
- Translational studies are warranted to explore the clinical efficacy of modulating Axin2 in patients with heart conditions.
