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

• Published in: JACC. Basic to translational science Vol. 5; no. 2; pp. 148 - 166
• Main Authors: Wang, Bin, Wang, Ze-Mu, Ji, Jia-Ling, Gan, Weihua, Zhang, Aiqing, Shi, Hao-Jie, Wang, Hao, Lv, Linli, Li, Zuolin, Tang, Taotao, Du, Jie, Wang, Xiaonan H., Liu, Bi-Cheng
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2020; Elsevier
• Subjects: Cardiovascular; exosome; FoxO3a; miR-155; PRECLINICAL RESEARCH; pyroptosis; uremic cardiomyopathy; FoxO; IL; uremic cardiomyopathy; FoxO3a; LV; miRs; pyroptosis; TUNEL; miR-155; AAV; 3’-UTRs; exosome; CKD; UCM; microRNAs; chronic kidney disease; 3’-untranslated regions; left ventricle; deoxyuridine triphosphate nick-end labeling; adeno-associated virus; forkhead transcription factors of the O class; interleukin; LV, left ventricle; 3’-UTRs, 3’-untranslated regions; AAV, adeno-associated virus; TUNEL, deoxyuridine triphosphate nick-end labeling; FoxO, forkhead transcription factors of the O class; IL, interleukin; miRs, microRNAs; UCM, uremic cardiomyopathy; CKD, chronic kidney disease
• 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.