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

• Type of Material: Article
• Authors: Bin Wang, Southeast University; Ze-Mu Wang, Nanjing Medical University; Jia-Ling Ji, Nanjing Medical University; Weihua Gan, Nanjing Medical University; Aiqing Zhang, Nanjing Medical University; Hao-Jie Shi, Nanjing Medical University; Hao Wang, Nanjing Medical University; Linli Lv, Southeast University; Zuolin Li, Southeast University; Taotao Tang, Southeast University; Jie Du, Capital Medical University; Xiaonan Wang, Emory University; Bi-Cheng Liu, Southeast University
• Language: English
• Date: 2020-02-01
• Publisher: Elsevier Science Inc.
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jacbts.2019.10.011
• Title of Journal or Parent Work: JACC: Basic to Translational Science
• Volume: 5
• Issue: 2
• Start Page: 148
• End Page: 166
• Grant/Funding Information: National Natural Science Foundation of China (No 81703213), the Natural Science Youth Foundation of Jiangsu Province of China (No. BK20151034) to Dr. Z.-M. Wang; This work was supported by grants from the National Natural Science Foundation of China (No 81700618), the Natural Science Foundation of Jiangsu Province (BK20181487), China Young Nephrologist Research Project, and Southeast University High Level Thesis Project to Dr. B. Wang; National Natural Science Foundation of China (No 81470922, 31671194, 81720108007, and 81670696)，National Key Research Program (2018YFC1314000) and Clinic Research Center of Jiangsu Province (BL2014080) to Dr. B.-C. Liu.
• Keywords: uremic cardiomyopathy; Endothelial cells; Fibrosis; miR-155; Cardiovascular System & Cardiology; Disease; Cardiac & Cardiovascular Systems; Gasdermin-D; Science & Technology; Fox03a; FOXO3A; Mechanisms; pyroptosis; Life Sciences & Biomedicine; exosome; Cardiac function; Transcription factors; Inflammation; Insulin
• Research Categories: Health Sciences, Pathology; Biology, Cell; Engineering, Biomedical

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.