SGLT2 inhibition ameliorates nano plastics-induced premature endothelial senescence and dysfunction.
Fiche publication
Date publication
avril 2023
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Pr SCHINI-KERTH Valérie
Tous les auteurs :
Dhakal B, Shiwakoti S, Park EY, Kang KW, Schini-Kerth VB, Park SH, Ji HY, Park JS, Ko JY, Oak MH
Lien Pubmed
Résumé
Nano plastics (NPs) have been a significant threat to human health and are known to cause premature endothelial senescence. Endothelial senescence is considered one of the primary risk factors contributing to numerous cardiovascular disorders. Recent studies have suggested that inhibition of sodium glucose co-transporter (SGLT2) ameliorates endothelial senescence and dysfunction. Therefore, our study intends to explore the role of SGLT2 in NPs-induced endothelial senescence and dysfunction. Porcine coronary artery and its endothelial cells were treated with NPs in the presence or absence of Enavogliflozin (ENA), a SGLT2 inhibitor and then SGLTs expression, senescence markers and vascular function were evaluated. NPs significantly up-regulated SGLT2 and ENA significantly decreased NPs-induced senescence-associated-β-gal activity, cell-cycle arrest, and senescence markers p53 and p21 suggesting that inhibition of SGLT2 prevents NPs-induced endothelial senescence. In addition, ENA decreased the formation of reactive oxygen species with the downregulation of Nox2, and p22. Furthermore, SGLT2 inhibition also up regulated the endothelial nitric oxide synthase expression along with improving vascular function. In conclusion, premature endothelial senescence by NPs is, at least in part, associated with SGLT2 and it could be a potential therapeutic target for preventing and/or treating environmental pollutants-induced cardiovascular disorders mediated by endothelial senescence and dysfunction.
Mots clés
Humans, Swine, Animals, Endothelial Cells, metabolism, Sodium-Glucose Transporter 2, genetics, Microplastics, metabolism, Cellular Senescence, physiology, Oxidative Stress, physiology
Référence
Sci Rep. 2023 04 17;13(1):6256