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

doi:10.1016/j.jacbts.2019.10.011

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

JACC Basic Transl Sci. 2020 Jan 15;5(2):148-166. doi: 10.1016/j.jacbts.2019.10.011. eCollection 2020 Feb.

Authors

Bin Wang¹, Ze-Mu Wang², Jia-Ling Ji³, Weihua Gan³, Aiqing Zhang³, Hao-Jie Shi², Hao Wang², Linli Lv¹, Zuolin Li¹, Taotao Tang¹, Jie Du⁴, Xiaonan H Wang⁵, Bi-Cheng Liu¹

Affiliations

¹ Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China.
² Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
³ Department of Pediatric Nephrology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
⁴ Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
⁵ Department of Medicine, Renal Division, Emory University, Atlanta, Georgia.

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.

Keywords: 3’-UTRs, 3’-untranslated regions; AAV, adeno-associated virus; CKD, chronic kidney disease; FoxO, forkhead transcription factors of the O class; FoxO3a; IL, interleukin; LV, left ventricle; TUNEL, deoxyuridine triphosphate nick-end labeling; UCM, uremic cardiomyopathy; exosome; miR-155; miRs, microRNAs; pyroptosis; uremic cardiomyopathy.