國家衛生研究院 NHRI:Item 3990099045/12227
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12227


    Title: Tryptophan metabolite 5-methoxytryptophan ameliorates arterial denudation-induced intimal hyperplasia via opposing effects on vascular endothelial and smooth muscle cells
    Authors: Chen, CH;Ho, YC;Ho, HH;Liang, LY;Jiang, WC;Lee, GL;Lee, JK;Hsu, YJ;Kuo, CC;Wu, KK;Yet, SF
    Contributors: Institute of Cellular and Systems Medicine
    Abstract: Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, particularly among older adults. Despite the advent of medical technology, restenosis is still an issue after interventional procedures. Tryptophan metabolite 5-methoxytryptophan (5-MTP) has recently been shown to protect against systemic inflammatory responses. This study aimed to investigate the function and mechanisms of 5-MTP in interventional procedure-induced restenosis. We found that after mouse femoral artery denudation with a guide wire, 5-MTP accelerated recovery of endothelium in the denuded area and reduced vascular leakage and intimal thickening. 5-MTP increased endothelial cell proliferation in the denuded arteries and rescued TNF-alpha-reduced endothelial cell proliferation and migration, likely via maintaining vascular endothelial growth factor receptor 2 activation. In contrast, 5-MTP preserved differentiated phenotype of medial vascular smooth muscle cells (VSMCs) and decreased VSMC proliferation and migration. Furthermore, 5-MTP maintained expression levels of critical transcription factors for VSMC marker gene expressions via attenuated activation of p38 MAPK and NFkappaB-p65. Our findings uncover a novel protective mechanism of 5-MTP in restenosis. In response to denudation injury, 5-MTP attenuates intimal hyperplasia via concerted but opposing actions on endothelial cells and VSMCs. Taken together, our results suggest that 5-MTP is a valuable therapeutic target for arterial injury-induced restenosis.
    Date: 2019-10-09
    Relation: Aging. 2019 Oct 9;11(19):8604-8622.
    Link to: http://dx.doi.org/10.18632/aging.102350
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1945-4589&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000490892100038
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85073648248
    Appears in Collections:[Shaw-Fang Yet] Periodical Articles
    [Kenneth Kun-Yu Wu] Periodical Articles
    [Cheng-Chin Kuo] Periodical Articles

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