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• W2767072475 endingPage "1223" @default.
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• W2767072475 abstract "Redox active ultrafine particles (UFP, d < 0.2 μm) promote vascular oxidative stress and atherosclerosis. Notch signaling is intimately involved in vascular homeostasis, in which forkhead box O1 (FOXO1) acts as a co-activator of the Notch activation complex. We elucidated the importance of FOXO1/Notch transcriptional activation complex to restore vascular regeneration after UFP exposure.In a zebrafish model of tail injury and repair, transgenic Tg(fli1:GFP) embryos developed vascular regeneration at 3 days post amputation (dpa), whereas UFP exposure impaired regeneration (p < 0.05, n = 20 for control, n = 28 for UFP). UFP dose dependently reduced Notch reporter activity and Notch signaling-related genes (Dll4, JAG1, JAG2, Notch1b, Hey2, Hes1; p < 0.05, n = 3). In the transgenic Tg(tp1:GFP; flk1:mCherry) embryos, UFP attenuated endothelial Notch activity at the amputation site (p < 0.05 vs. wild type [WT], n = 20). A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) inhibitor or dominant negative (DN)-Notch1b messenger RNA (mRNA) disrupted the vascular network, whereas notch intracellular cytoplasmic domain (NICD) mRNA restored the vascular network (p < 0.05 vs. WT, n = 20). UFP reduced FOXO1 expression, but not Master-mind like 1 (MAML1) or NICD (p < 0.05, n = 3). Immunoprecipitation and immunofluorescence demonstrated that UFP attenuated FOXO1-mediated NICD pull-down and FOXO1/NICD co-localization, respectively (p < 0.05, n = 3). Although FOXO1 morpholino oligonucleotides (MOs) attenuated Notch activity, FOXO1 mRNA reversed UFP-mediated reduction in Notch activity to restore vascular regeneration and blood flow (p < 0.05 vs. WT, n = 5). Innovation and Conclusion: Our findings indicate the importance of the FOXO1/Notch activation complex to restore vascular regeneration after exposure to the redox active UFP. Antioxid. Redox Signal. 28, 1209-1223." @default.
• W2767072475 created "2017-11-10" @default.
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• W2767072475 date "2018-05-01" @default.
• W2767072475 modified "2023-10-16" @default.
• W2767072475 title "Ultrafine Particle Exposure Reveals the Importance of FOXO1/Notch Activation Complex for Vascular Regeneration" @default.
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• W2767072475 doi "https://doi.org/10.1089/ars.2017.7166" @default.
• W2767072475 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5912723" @default.
• W2767072475 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29037123" @default.
• W2767072475 hasPublicationYear "2018" @default.
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