Exosomes derived from oxLDL-stimulated macrophages induce neutrophil extracellular traps to drive atherosclerosis

This study aimed to investigate the role and underlying mechanism of exosomes secreted by oxidized low-density lipoprotein (oxLDL)-stimulated macrophages in the progression of atherosclerosis (AS). Exosomes from peripheral blood of AS patients or oxLDL-treated macrophages were co-cultured with human...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Cell cycle (Georgetown, Tex.) Ročník 18; číslo 20; s. 2672 - 2682
Hlavní autoři: Zhang, Yong-Gan, Song, Yan, Guo, Xue-Li, Miao, Ren-Ying, Fu, Yi-Qun, Miao, Chao-Feng, Zhang, Chuang
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Taylor & Francis 18.10.2019
Témata:
Atherosclerosis
exosomes
macrophages
neutrophil extracellular traps
oxidized low-density lipoprotein
Research Paper
macrophages
neutrophil extracellular traps
oxidized low-density lipoprotein
exosomes
Atherosclerosis
ISSN:1538-4101, 1551-4005, 1551-4005
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí:This study aimed to investigate the role and underlying mechanism of exosomes secreted by oxidized low-density lipoprotein (oxLDL)-stimulated macrophages in the progression of atherosclerosis (AS). Exosomes from peripheral blood of AS patients or oxLDL-treated macrophages were co-cultured with human neutrophils. Neutrophil extracellular traps (NETs) were detected by immunofluorescence staining. The levels of inflammatory cytokines were quantified by enzyme-linked immunosorbent assay (ELISA). The expression levels of miR-146a and superoxide dismutase 2 (SOD2) were determined by quantitative real-time PCR (qRT-PCR) and western blot. The generation of intracellular reactive oxygen species (ROS) was observed by using dichlorofluorescin diacetate (DCFH-DA). ApoE-deficient mice were fed with high-fat diet (HFD) to induce AS. Atherosclerotic plaques were evaluated by Oil red O (ORO) and hematoxylin-eosin (HE) staining. Our results showed that miRNA-146a was enriched in serum-derived exosomes of AS patients and oxLDL-treated macrophage THP-1-derived exosomes. Importantly, exosomal miR-146a secreted by oxLDL-treated macrophages promoted ROS and NETs release via targeting SOD2. In addition, intravenous administration of oxLDL-treated THP-1 cells-derived exosomes into AS mice significantly deteriorated AS in vivo. Our findings indicate that exosomal miR-146a derived from oxLDL-treated macrophages promotes NETs formation via inducing oxidative stress, which might provide a novel scientific basis for the understanding of AS progression.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1538-4101
1551-4005
1551-4005
DOI:10.1080/15384101.2019.1654797