期刊
CARDIOVASCULAR TOXICOLOGY
卷 22, 期 6, 页码 592-601出版社
HUMANA PRESS INC
DOI: 10.1007/s12012-022-09740-y
关键词
Endothelial senescence; miR-21; Exosomes; H2O2; P53; P21
Exosomes from senescence cells have been found to play important roles in endothelium dysfunction. In this study, we investigated the cargo of exosomes released by endothelial cells undergoing senescence in vitro. We found that these exosomes have distinct miRNA and protein expression profiles, and can affect the migration rate of endothelial cells.
Exosomes from senescence cells play pivotal roles in endothelium dysfunction. We investigated the exosomal angiogenic cargo of endothelial cells (ECs) in a model of senescence in vitro. After inducing aging by H2O2, the expression of P53, P21, and P16 was investigated by western blotting, while the expression of FMR1, miR-21, and miR-126 were measured by real-time PCR (q-PCR). Oil Red O dye was used to stain cells. Acetylcholinesterase (AChE) assay, transmission electron microscopy (TEM), and western blotting characterized Exosomes. Exosomal miR-21, miR-126, matrix metallopeptidase-9 (MMP-9), and tumor necrosis factor- alpha (TNF-alpha) proteins were measured by Q-PCR and western blotting. A wound-healing assay was used to explore the effect of exosomes on ECs migration rate. The results showed that the expression of P53, P21, P16, FMR1, and miR-21 was increased in treated cells as compared with control cells (P < 0.05). In addition, the expression of miR-126 was decreased in treated cells (P < 0.05). The number of Oil Red O-positive-treated cells increased (P < 0.05). The AChE activity of exosomes from treated cells was increased (P < 0.05). In comparison with control cells, an increase in the expression levels of exosomal miR-21 and TNF-alpha of treated cells coincided with a decrease in the expression levels of miR-126 and MMP-9 levels (P < 0.05). We found that the migration rate of ECs co-cultured with exosomes from treated cells was decreased (P < 0.05). The data indicate ECs under H2O2 condition produce exosomes with distinct cargo that may be useful as a biomarker of age-related vascular disease.
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