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- W3176042301 abstract "Rationale The E-selectin in endothelium promotes the growth of atherosclerotic plaques. We identified an E-selectin-targeting thioaptamer (ESTA) and conjugated it onto a multistage vector (MSV) to form an ESTA-MSV microparticle. We tested E-selectin-targeted delivery of microRNAs (miRs) for the treatment of atherosclerosis. Methods and Results The E-selectin was up-regulated, while the miR-146a and miR-181b were down-regulated, in TNF-α-treated human microvascular endothelial cells (HMVECs). MiR-146a and miR-181b mimics were packaged into the ESTA-MSV. Both miR-146a and miR-181b attenuated TNF-α-induced endothelial inflammation. Moreover, the monocyte adhesion to HMVECs was also attenuated by miR-146a or miR-181b. The ApoE-/- mice were injected with ESTA-MSV-packaged miR-146a or miR-181b biweekly through tail vein for 12 weeks. Injection of miR mimics resulted in a 4.7- and 5.7-fold overexpression of miRs in mouse aortas. The immunofluorescence staining showed the co-localization of E-selectin and miRs in aortic endothelium. MiR-146a and miR-181b significantly inhibited atherosclerotic lesion size, lipids deposition, macrophage and lymphocyte infiltration in plaques, and expression of adhesion molecules in aortas. Conclusions E-selectin-targeting delivery of miR-146a and miR-181b to inflamed endothelium inhibits atherosclerosis. These findings provide a novel delivery system for miR-based therapy of atherosclerosis." @default.
- W3176042301 created "2021-07-05" @default.
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- W3176042301 date "2015-04-01" @default.
- W3176042301 modified "2023-10-18" @default.
- W3176042301 title "Targeted delivery of microRNAs by microparticles to inflamed endothelium ameliorates endothelial inflammation and atherosclerosis" @default.
- W3176042301 doi "https://doi.org/10.1096/fasebj.29.1_supplement.lb580" @default.
- W3176042301 hasPublicationYear "2015" @default.
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