Exosomes derived from oxLDL-stimulated macrophages induce neutrophil extracellular traps to drive atherosclerosis.
Cell Cycle
; 18(20): 2674-2684, 2019 Oct.
Article
en En
| MEDLINE
| ID: mdl-31416388
ABSTRACT
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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Aterosclerosis
/
Exosomas
/
Trampas Extracelulares
/
Lipoproteínas LDL
/
Macrófagos
/
Neutrófilos
Límite:
Aged
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Cell Cycle
Año:
2019
Tipo del documento:
Article
País de afiliación:
China