Intracellular glutamine level determines vascular smooth muscle cell-derived thrombogenicity
Shohei Koyama1, Atsushi Yamashita2, Yunosuke Matsuura3
1Department of Pathology, Faculty of Medicine, University of Miyazaki, Japan; Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Japan.
Atherosclerosis
|June 8, 2021
Summary
Everolimus-eluting stents (EES) reduce stent thrombosis by increasing intracellular glutamine levels in vascular smooth muscle cells. This mechanism enhances vascular metabolism and reduces thrombogenicity, independent of mTOR pathway activity.
Area of Science:
- Cardiovascular Research
- Biomedical Engineering
- Metabolomics
Background:
- In-stent restenosis (ISR) is a complication of coronary interventions.
- Everolimus-eluting stents (EES) are effective for ISR and show reduced stent thrombosis.
- The mechanism behind EES's reduced thrombogenicity is not fully understood.
Purpose of the Study:
- To investigate the effects of everolimus on vascular metabolism and thrombogenicity.
- To elucidate the mechanistic link between everolimus, metabolism, and stent thrombosis.
Main Methods:
- Implantation of EES and bare-metal stents in rabbit iliac arteries.
- Histological analysis and metabolomics of stented arteries.
- In vitro assessment of everolimus effects on smooth muscle cell (SMC) metabolism, tissue factor (TF) expression, and procoagulant activity.
Main Results:
- EES implantation reduced neointima formation, SMC infiltration, and TF expression.
- EES-treated arteries showed increased levels of amino acid metabolites, notably glutamine.
- In vitro, everolimus increased intracellular glutamine, decreased TF expression, and reduced procoagulant activity in SMCs.
Conclusions:
- Intracellular glutamine levels appear to dictate SMC thrombogenicity, irrespective of mTOR pathway activity.
- Elevated intracellular glutamine may contribute to the reduced stent thrombosis observed with EES use.
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