Intracellular glutamine level determines vascular smooth muscle cell-derived thrombogenicity
| Autor: | Yusuke Saito, Kazuo Kitamura, Toshihiro Gi, Yujiro Asada, Yunosuke Matsuura, Kazunari Maekawa, Shohei Koyama, Atsushi Yamashita |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Neointima Vascular smooth muscle Glutamine Myocytes Smooth Muscle Thrombogenicity 030204 cardiovascular system & hematology Pharmacology Prosthesis Design Muscle Smooth Vascular Coronary Restenosis 03 medical and health sciences Percutaneous Coronary Intervention 0302 clinical medicine Restenosis medicine Animals PI3K/AKT/mTOR pathway Everolimus Chemistry Cardiovascular Agents Drug-Eluting Stents medicine.disease 030104 developmental biology Rabbits Cardiology and Cardiovascular Medicine Intracellular medicine.drug |
| Zdroj: | Atherosclerosis. 328:62-73 |
| ISSN: | 0021-9150 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect