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 cocultured 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.
AIM:To study the risk factors for morbidity and mortality following total gastrectomy. METHODS: We retrospectively reviewed the records of 125 consecutive patients who underwent total gastrectomy for gastric cancer at the Second Affiliated Hospital of Zhejiang University School of Medicine between January 2003 and March 2008. RESULTS: The overall morbidity rate was 20.8% (27 patients) and the mortality rate was 3.2% (4 patients). Morbidity rates were higher in patients aged over 60 [odds ratio (OR)
Atherosclerosis is one of the most prevalent and important cardiac diseases, involving the heart and brain. This study aimed to explore the impacts of lncRNA Divergent to GSC induced by TGF-b family signaling (DIGIT) on vascular endothelial cells tube-formation capacity so as to reveal the potentials of DIGIT in atherosclerosis therapy. DIGIT expression in human microvascular endothelial HMEC-1 cells was silenced by transfection with shRNAs-targeted DIGIT. The effects of DIGIT silence on cell viability, migration, apoptosis, and tube formation were then assessed. Additionally, the cross-regulation between DIGIT and miR-134, and between miR-134 and Bmi-1 was detected to further reveal through which mechanism (s) DIGIT mediated HMEC-1 cells. The results showed that DIGIT silence significantly reduced cell viability, migration, tube-like structures formation, and induced apoptosis in HMEC-1 cells. DIGIT worked as a sponge for miR-134, and the anti-growth, anti-migratory, and anti-tube-formation functions of DIGIT silence on HMEC-1 cells were abolished by miR-134 suppression. Bmi-1 was a target of miR-134, and Bmi-1 upregulation abolished miR-134 overexpression-diminished cell growth, migration, and tube formation of HMEC-1 cells. Furthermore, Bmi-1 upregulation activated PI3K/AKT and Notch signaling pathways. In conclusion, our study demonstrated that lncRNA DIGIT accelerated tube formation of vascular endothelial cells through sponging miR-134. Our findings suggest that DIGIT and miR-134 may be promising molecular targets for atherosclerosis therapy.
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