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• W2959636855 abstract "Abstract We hypothesized that NADPH oxidase 4 (Nox4) is involved in the formation of neointimal atherosclerotic plaques through the migration of smooth muscle cells (SMCs) in response to flagellin. Here, we demonstrate that TLR5-mediated Nox4 activation regulates the migration of SMCs, leading to neointimal plaque formation in atherosclerosis. To investigate the molecular mechanism by which the TLR5-Nox4 cascade mediates SMC migration, we analyzed the signaling cascade in primary vascular SMCs (VSMCs) from wild-type (WT) or Nox4 KO mice. Stimulation of VSMCs from Nox4 KO mice with flagellin failed to induce H 2 O 2 production and Rac activation compared with stimulation of VSMCs from WT mice. Moreover, the migration of Nox4-deficient VSMCs was attenuated in response to flagellin in transwell migration and wound healing assays. Finally, we performed partial carotid artery ligation in ApoE KO and Nox4ApoE DKO mice fed a high-fat diet (HFD) with or without recombinant FliC (rFliC) injection. Injection of rFliC into ApoE KO mice fed a HFD resulted in significantly increased SMC migration into the intimal layer, whereas SMC accumulation was not detected in Nox4ApoE DKO mice. We conclude that activation of the TLR5-Nox4 cascade plays an important role in the formation of neointimal atherosclerotic plaques." @default.
• W2959636855 created "2019-07-23" @default.
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• W2959636855 date "2019-07-01" @default.
• W2959636855 modified "2023-10-12" @default.
• W2959636855 title "The flagellin-TLR5-Nox4 axis promotes the migration of smooth muscle cells in atherosclerosis" @default.
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• W2959636855 doi "https://doi.org/10.1038/s12276-019-0275-6" @default.
• W2959636855 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6802658" @default.
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