Macrophage-Derived Exosomal Mir-155 Regulating Cardiomyocyte Pyroptosis and Hypertrophy in Uremic Cardiomyopathy

• Published in: JACC. Basic to translational science 2020-02, Vol.5 (2), p.148-166
• Main Authors: Wang, Bin, MD, PhD, Wang, Ze-Mu, MD, PhD, Ji, Jia-Ling, MD, Gan, Weihua, PhD, Zhang, Aiqing, PhD, Shi, Hao-Jie, MD, Wang, Hao, PhD, Lv, Linli, MD, Li, Zuolin, MD, Tang, Taotao, MD, Du, Jie, PhD, Wang, Xiaonan H., MD, Liu, Bi-Cheng, MD, PhD
• Format: Article
• Language: English
• Subjects: Cardiovascular; exosome; FoxO3a; miR-155; PRECLINICAL RESEARCH; pyroptosis; uremic cardiomyopathy
• ISSN: 2452-302X; 2452-302X
• DOI: 10.1016/j.jacbts.2019.10.011

[Display omitted] •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 in cardiomyocytes.•Macrophage-derived miR-155–containing exosomes promoted cardiomyocyte pyroptosis and uremic cardiomyopathy changes (cardiac hypertrophy and fibrosis) by directly targeting FoxO3a in uremic mice. Inhibiting secretion from macrophage-derived miR-155–containing exosomes represents a novel therapeutic strategy for the management of uremic cardiomyopathy. 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.