論文

国際誌
2021年7月

Intracellular glutamine level determines vascular smooth muscle cell-derived thrombogenicity.

Atherosclerosis
  • Shohei Koyama
  • ,
  • Atsushi Yamashita
  • ,
  • Yunosuke Matsuura
  • ,
  • Yusuke Saito
  • ,
  • Kazunari Maekawa
  • ,
  • Toshihiro Gi
  • ,
  • Kazuo Kitamura
  • ,
  • Yujiro Asada

328
開始ページ
62
終了ページ
73
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.atherosclerosis.2021.05.012

BACKGROUND AND AIMS: The everolimus-eluting stent (EES), one of the effective stents for in-stent restenosis (ISR), has a lower incidence of stent thrombosis; however, the underlying mechanism remains unknown. This study aimed to identify the effects of everolimus on vascular metabolism and thrombogenicity and examine their mechanistic link. METHODS: EESs and bare-metal stents were implanted in rabbit iliac arteries with smooth muscle cell (SMC)-rich neointima induced by endothelial denudation. Four weeks after stent implantation, the stented arteries were examined for histological analysis and metabolomics. Additionally, everolimus effects in coronary artery SMCs metabolism, tissue factor (TF) expression, and procoagulant activity were assessed in vitro. RESULTS: EES-implanted arteries showed decreased neointima formation, less SMCs infiltration, and reduced TF expression. Concomitantly, they were metabolically characterized by increased levels of metabolites in amino acids, such as glutamine. Similarly, everolimus increased intracellular glutamine levels, decreased TF expression, and reduced procoagulant activity in SMCs in vitro. On the contrary, exogenous glutamine administration also increased intracellular glutamine level, decreased TF expression, and reduced procoagulant activity despite enhanced mammalian target of rapamycin (mTOR) activity. CONCLUSIONS: Intracellular glutamine level is likely to determine vascular SMC-related thrombogenicity regardless of mTOR pathway activity. Therefore, increased intracellular glutamine level might contribute partially to the beneficial effect of EES use on stent thrombosis.

リンク情報
DOI
https://doi.org/10.1016/j.atherosclerosis.2021.05.012
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/34102425
ID情報
  • DOI : 10.1016/j.atherosclerosis.2021.05.012
  • PubMed ID : 34102425

エクスポート
BibTeX RIS