Research Paper Volume 13, Issue 8 pp 12239—12257
Extracellular-vesicle containing miRNA-503-5p released by macrophages contributes to atherosclerosis
- 1 Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, P. R. China
- 2 Department of Pharmacy, North Sichuan Medical College, Nanchong 637000, P. R. China
- 3 Department of Thoracic Surgery, Dazhou Central Hospital, Dazhou 635000, P. R. China
- 4 School 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, 2020 Accepted: May 27, 2020 Published: April 19, 2021https://doi.org/10.18632/aging.103855
How to Cite
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.
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.
ECs: endothelial cells; SMCs: smooth muscle cells; ox-LDL: oxidized low-density lipoprotein; EVs: Extracellular vesicles; mRNAs: messenger RNAs; miRs/miRNAs: microRNAs; TGF-β: transforming growth factor-β; HCA: human coronary artery; VSMCs: vascular smooth muscle cells; RT-qPCR: reverse transcription-quantitative polymerase chain reaction; NC: negative control; CCK-8: cell counting kit-8; WT: wild-type; MUT: mutant-type; TEM: transmission electron microscope; NTA: Nanoparticle tracking analyzer; ATCC: American Type Culture Collection; RPMI: Royal Park Memorial Institute; FBS: fetal bovine serum; DMEM: Dulbecco’s modified Eagle’s medium; p: phospho; ELISA: Enzyme-linked immunosorbent assay; ANOVA: analysis of variance.