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Exosomal miR‐512‐3p derived from mesenchymal stem cells inhibits oxidized low‐density lipoprotein‐induced vascular endothelial cells dysfunction via regulating Keap1
Author(s) -
Chen Sisi,
Zhou Heng,
Zhang Bofang,
Hu Qi
Publication year - 2021
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22767
Subject(s) - microvesicles , mesenchymal stem cell , keap1 , oxidative stress , microbiology and biotechnology , chemistry , downregulation and upregulation , cancer research , tumor necrosis factor alpha , apoptosis , stem cell , gene silencing , microrna , biology , immunology , biochemistry , transcription factor , gene
Atherosclerosis (AS) is a prevalent chronic inflammatory vascular disease. Upregulated oxidized low‐density lipoprotein (ox‐LDL) in the serum has been found to induce endothelial cells (ECs) apoptosis by increasing oxidative stress and promoting inflammatory response, which are essential mechanisms of AS development. Mesenchymal stem cells (MSCs), which secrete exosomes to transport microRNAs (miRNAs) and regulate cell functions, have become a research focus in recent years. The results of this study manifested that MSCs‐derived exosomes were phagocytosed by EC. In addition, miR‐512‐3p enriched by MSCs‐ derived exosomes markedly inhibited ox‐LDL‐mediated EC damage, namely, accelerated EC proliferation, inhibited Caspase‐3 activation and cell apoptosis, inhibited the levels of inflammatory cytokines (tumor necrosis factor‐α, interleukin (IL)‐1β, and IL‐6) and oxidative factor MDA, and increased the contents of SOD and GSH‐PX. Mechanistically, Keleh‐like ECH‐associated protein 1 (Keap1) was proved to be a functional target of miR‐512‐3p. Furthermore, silencing Keap1 limited ox‐LDL‐mediated EC cell dysfunction, while over‐expressing Keap1 mitigated the exosomal miR‐512‐3p‐mediated protective effect in Ox‐LDL‐induced EC. The above results confirmed that miR‐512‐3p shuttled by MSCs‐derived exosomes protected EC against ox‐LDL by targeting Keap1.