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Glut10 restrains neointima formation by promoting SMCs mtDNA demethylation and improving mitochondrial function.

Authors :
Wu Q
Hu Z
Wang Z
Che Y
Zhang M
Zheng S
Xing K
Zhong X
Chen Y
Shi F
Yuan S
Source :
Translational research : the journal of laboratory and clinical medicine [Transl Res] 2023 Oct; Vol. 260, pp. 1-16. Date of Electronic Publication: 2023 May 21.
Publication Year :
2023

Abstract

Neointimal hyperplasia is a major clinical complication of coronary artery bypass graft and percutaneous coronary intervention. Smooth muscle cells (SMCs) play a vital roles in neointimal hyperplasia development and undergo complex phenotype switching. Previous studies have linked glucose transporter member 10(Glut10) to the phenotypic transformation of SMCs. In this research, we reported that Glut10 helps maintain the contractile phenotype of SMCs. The Glut10-TET2/3 signaling axis can arrest neointimal hyperplasia progression by improving mitochondrial function via promotion of mtDNA demethylation in SMCs. Glut10 is significantly downregulated in both human and mouse restenotic arteries. Global Glut10 deletion or SMC-specific Glut10 ablation in the carotid artery of mice accelerated neointimal hyperplasia, while Glut10 overexpression in the carotid artery triggered the opposite effects. All of these changes were accompanied by a significant increase in vascular SMCs migration and proliferation. Mechanistically, Glut10 is expressed primarily in the mitochondria after platelet-derived growth factor-BB (PDGF-BB) treatment. Glut10 ablation induced a reduction in ascorbic acid (VitC) concentrations in mitochondria and mitochondrial DNA (mtDNA) hypermethylation by decreasing the activity and expression of the Ten-eleven translocation (TET) protein family. We also observed that Glut10 deficiency aggravated mitochondrial dysfunction and decreased the adenosinetriphosphate (ATP) content and the oxygen consumption rate, which also caused SMCs to switch their phenotype from contractile to synthetic phenotype. Furthermore, mitochondria-specific TET family inhibition partially reversed these effects. These results suggested that Glut10 helps maintain the contractile phenotype of SMCs. The Glut10-TET2/3 signaling axis can arrest neointimal hyperplasia progression by improving mitochondrial function via the promotion of mtDNA demethylation in SMCs.<br /> (Copyright © 2023 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1878-1810
Volume :
260
Database :
MEDLINE
Journal :
Translational research : the journal of laboratory and clinical medicine
Publication Type :
Academic Journal
Accession number :
37220836
Full Text :
https://doi.org/10.1016/j.trsl.2023.05.001