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Research Paper|Volume 13, Issue 8|pp 12239—12257

Extracellular-vesicle containing miRNA-503-5p released by macrophages contributes to atherosclerosis

Yuquan Wang1, Zhengmin Xu2, Xiaoli Wang2, Jiankang Zheng1, Lihan Peng1, Yunfei Zhou3, Yongyan Song4, Zhan Lu1
  • 1Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, P. R. China
  • 2Department of Pharmacy, North Sichuan Medical College, Nanchong 637000, P. R. China
  • 3Department of Thoracic Surgery, Dazhou Central Hospital, Dazhou 635000, P. R. China
  • 4School of Preclinical Medicine, and Nanchong Key Laboratory of Metabolic Drugs and Biological Products, North Sichuan Medical College, Nanchong 637000, P. R. China
Received: February 17, 2020Accepted: May 27, 2020Published: April 19, 2021
https://doi.org/10.18632/aging.103855

Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Endothelial dysfunction, and the differentiation of smooth muscle cells (SMCs) into proliferative, secretory phenotypes, are two major pathophysiological processes in atherosclerosis. SMCs have the potential to recruit macrophages in atherosclerotic plaques, in which macrophages drive inflammatory responses. In this study, we found that microRNA-503-5p (miR-503-5p) was enriched in either extracellular vesicles (EVs), secreted by oxidized low-density lipoprotein-treated macrophages, or the EVs from peripheral blood mononuclear cells of atherosclerosis patients. miR-503-5p was transferred intercellularly from macrophages to the co-cultured human coronary artery endothelial cells (HCAECs) and HCASMCs via EVs, thus reducing the proliferative and angiogenic abilities of HCAECs and accelerating the proliferative and migrating abilities of HCASMCs. Smad family members 1, 2 and 7 were negatively regulated by miR-503-5p in HCAECs and HCASMCs. miR-503-5p was verified as an enhancer of inflammatory cytokines and adhesion molecules released by macrophages, in part via the down-regulation of smad family members 1, 2 and 7. The inhibition of miR-503-5p by lentivirus reduced atherosclerotic lesion formations in the aorta of atherosclerotic mice. Our work demonstrated a miR-503-5p- and EV-mediated mechanism for macrophage communication with HCAECs and HCASMCs in atherosclerosis. miR-503-5p is pro-atherosclerotic stimuli that may be a therapeutic target for atherosclerosis treatment.