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

Bin, Wang, Ze-Mu, Wang, Jia-Ling, Ji, Weihua, Gan, Aiqing, Zhang, Hao-Jie, Shi, Hao, Wang, Linli, Lv, Zuolin, Li, Taotao, Tang, Jie, Du, Xiaonan H., Wang, Bi-Cheng, Liu

JACC: Basic to Translational Science |

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.