Harari, Emanuel; Guo, Liang; Smith, Samantha L.; Paek, Ka Hyun; Fernandez, Raquel; Sakamoto, Atsushi; Mori, Hiroyoshi; Kutyna, Matthew D.; Habib, Anwer; Torii, Sho; Cornelissen, Anne; Jinnouchi, Hiroyuki; Gupta, Anuj; Kolodgie, Frank D.; Virmani, Renu; Finn, Aloke V. published the artcile< Direct Targeting of the mTOR (Mammalian Target of Rapamycin) Kinase Improves Endothelial Permeability in Drug-Eluting Stents-Brief Report>, Related Products of 1223001-51-1, the main research area is atherosclerosis mTOR kinase endothelial permeability drug eluting stent; animals; atherosclerosis; drug-eluting stents; endothelium; rabbits; stents.
We recently showed that canonical mTOR inhibitors bind FKBP12.6, displace it from calcium release channels, resulting in activation of PKCa (protein kinase Ca) and dissociation of p-120-catenin (p120) from vascular endothelial cadherin; promoting endothelial barrier dysfunction. However, the relevance of these findings to drug-eluting stents remains unknown. Newer generation direct mTOR kinase inhibitors do not bind FKBP12.6 and offer the potential of improving endothelial barrier function while maintaining antirestenotic efficacy, but their actual effects are unknown. We examined the effects of 2 different pharmacol. targeting strategies-canonical mTOR inhibitor everolimus and mTOR kinase inhibitors Torin-2-on EBD after stenting. At 60 days after stent placement, everolimus-eluting stents demonstrated large areas of Evans blue dye staining and evidence of p120 VE-CAD dissociation consistent with EBD. As proof of concept of the role of EBD in neoatherosclerosis, 100 days after stenting, animals were fed an enriched cholesterol diet for an addnl. 30 days. Everolimus-eluting stents demonstrated significantly more macrophage infiltration (consistent with neoatherosclerosis) compared with both bare metal stents and Torin-2-eluting stent. Our results pinpoint interactions between FKBP12.6 and canonical mTOR inhibitors as a major cause of vascular permeability and neoatherosclerosis, which can be overcome by using mTOR kinase inhibitors.
Arteriosclerosis, Thrombosis, and Vascular Biology published new progress about Atherosclerosis. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Related Products of 1223001-51-1.
Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem