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Published on: April 10, 2019
Macrophage-Derived Exosomal Mir-155 Regulating Cardiomyocyte Pyroptosis and Hypertrophy in Uremic Cardiomyopathy
Bin Wang1, Ze-Mu Wang2, Jia-Ling Ji3
1Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China.
Abstract:
miR-155 was synthesized and loaded into exosomes in increased infiltration of macrophages in a uremic heart. The released exosomal fusion with the plasma membrane leads to the release of miR-155 into the cytosol and translational repression of forkhead transcription factors of the O class (FoxO3a) in cardiomyocytes. Finally, macrophage-derived miR-155-containing exosomes promoted cardiomyocyte pyroptosis and uremic cardiomyopathy changes (cardiac hypertrophy and fibrosis) by directly targeting FoxO3a in uremic mice.
Insights
Macrophage-derived exosomes carrying miR-155 promote uremic cardiomyopathy by targeting FoxO3a in heart cells. This leads to pyroptosis, cardiac hypertrophy, and fibrosis in uremic mice.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Exosome Biology
Background:
- Uremic cardiomyopathy is characterized by cardiac hypertrophy and fibrosis.
- Macrophage infiltration is increased in the uremic heart.
- MicroRNAs (miRNAs) play crucial roles in cardiovascular diseases.
Purpose of the Study:
- To investigate the role of exosomal miR-155 derived from macrophages in the pathogenesis of uremic cardiomyopathy.
- To elucidate the molecular mechanism by which miR-155 affects cardiomyocytes in a uremic environment.
Main Methods:
- Isolation and characterization of exosomes from macrophages.
- In vivo studies using a mouse model of uremic cardiomyopathy.
- Analysis of miR-155 expression, exosome release, and target gene regulation (FoxO3a).
- Assessment of cardiomyocyte pyroptosis, cardiac hypertrophy, and fibrosis.
Main Results:
- Macrophage-derived exosomes were found to contain increased levels of miR-155 in uremic conditions.
- Exosomal miR-155 was transferred to cardiomyocytes, leading to translational repression of FoxO3a.
- Targeting of FoxO3a by miR-155 promoted cardiomyocyte pyroptosis.
- Macrophage-derived exosomal miR-155 exacerbated cardiac hypertrophy and fibrosis in uremic mice.
Conclusions:
- Macrophage-derived exosomal miR-155 is a key mediator in the development of uremic cardiomyopathy.
- The mechanism involves the targeting of FoxO3a, leading to pyroptosis and adverse cardiac remodeling.
- Exosomes represent a potential therapeutic target for mitigating uremic cardiomyopathy.
