國家衛生研究院 NHRI:Item 3990099045/16103
English  |  正體中文  |  简体中文  |  全文筆數/總筆數 : 12145/12927 (94%)
造訪人次 : 912494      線上人數 : 1202
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜尋範圍 查詢小技巧：
  • 您可在西文檢索詞彙前後加上"雙引號"，以獲取較精準的檢索結果
  • 若欲以作者姓名搜尋，建議至進階搜尋限定作者欄位，可獲得較完整資料
    •  進階搜尋
    主頁 ‧ 登入 ‧ 上傳 ‧ 說明 ‧ 關於NHRI ‧ 管理 到手機版


    請使用永久網址來引用或連結此文件: http://ir.nhri.org.tw/handle/3990099045/16103


    題名: The role of hydroxyindole o-methyltransferase in vascular remodeling and tryptophan metabolism
    作者: Jiang, WC;Yet, SF
    貢獻者: Institute of Cellular and Systems Medicine
    摘要: Background and Aims: Tryptophan is an essential amino acid and an important source for protein synthesis, and its various metabolites also participate in diverse physiological functions. We have previously shown that one of the tryptophan metabolites, 5-methoxytryptophan (5-MTP), reduces inflammatory cytokine-induced p38 MAPK activation in vascular smooth muscle cells (VSMCs) and protects against vascular remodeling in animal models. Our goal is to investigate whether hydroxyindole O-methyltransferase (HIOMT) is the synthetic enzyme for 5-MTP and functions as 5-MTP in protecting against intimal hyperplasia and whether it alters tryptophan metabolism in VSMCs. Methods: HIOMT transgenic mice were generated to evaluate the function of HIOMT in vivo using a neointima formation model. Immunohistochemistry was performed to evaluate intimal hyperplasia and expression levels of select tryptophan metabolites. Primary wild-type and transgenic VSMCs were used in vitro for mechanistic studies. Results: Compared with wild-type, HIOMT transgenic mice had increased 5-MTP levels in the medial layer of the arteries. After arterial injury, transgenic mice had smaller neointima and reduced MMP2 levels in the arterial wall. Furthermore, arterial levels of the tryptophan metabolite serotonin and its synthetic enzyme aromatic amino acid decarboxylase (AADC) were lower than those of wild-types. Interestingly, serotonin promotes VSMC proliferation and reduces the expression of VSMC markers. Transient transfection of HIOMT expression plasmid in VSMCs or primary HIOMT transgenic VSMCs exhibited higher 5-MTP levels, reduced IL1-β-induced p38 phosphorylation, and prevented IL1-β-reduced VSMC marker downregulation. Moreover, HIOMT overexpression decreased basal and IL1-β-induced serotonin and AADC levels in VSMCs. Conclusions: Our results indicate that HIOMT is the synthetic enzyme of 5-MTP in VSMCs and protects against injury-induced occlusive vascular disease. Tryptophan metabolic pathways are altered in VSMCs when 5-MTP is present, or HIOMT is overexpressed. Taken together, 5-MTP and its synthetic enzyme HIOMT are important targets for treating occlusive vascular disease.
    日期: 2024-08
    關聯: Atherosclerosis. 2024 Aug;395(Suppl. 1):Meeting Abstract 118262.
    Link to: https://doi.org/10.1016/j.atherosclerosis.2024.118262
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0021-9150&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001301179200067
    顯示於類別:[林秀芳] 會議論文/會議摘要

    文件中的檔案:

    檔案 描述 大小格式瀏覽次數
    ISI001301179200067.pdf60KbAdobe PDF18檢視/開啟


    在NHRI中所有的資料項目都受到原著作權保護.

    TAIR相關文章

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - 回饋