title: Curcumin Attenuates Rapamycin-induced Cell Injury of Vascular Endothelial Cells.
abstract: Although drug-eluting stents (DES) effectively improve the clinical efficacy of percutaneous coronary intervention, a high risk of late stent thrombosis and in-stent restenosis also exists after DES implantation. Anti-smooth muscle proliferation drugs, such as rapamycin, coating stents, not only inhibit the growth of vascular smooth muscle cells but also inhibit vascular endothelial cells and delay the reendothelialization. Therefore, the development of an ideal agent that protects vascular endothelial cells from rapamycin-eluting stents is of great importance for the next generation of DES. In this study, we demonstrated that rapamycin significantly inhibited the growth of rat aortic endothelial cells in both dose- and time-dependent manner in vitro. Cell apoptosis was increased and migration was decreased by rapamycin treatments in rat aortic endothelial cells in vitro. Surprisingly, treatment with curcumin, an active ingredient of turmeric, significantly reversed these detrimental effects of rapamycin. Moreover, curcumin increased the expression of vascular nitric oxide synthases (eNOS), which was decreased by rapamycin. Furthermore, caveolin-1, the inhibitor of eNOS, was decreased by curcumin. Knockdown of eNOS by small interfering RNA significantly abrogated the protective effects of curcumin. Taken together, our results suggest that curcumin antagonizes the detrimental effect of rapamycin on aortic endothelial cells in vitro through upregulating eNOS. Therefore, curcumin is a promising combined agent for the rescue of DES-induced reendothelialization delay.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Guo
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Chen
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fang
authors.forename: Hongbing
authors.initials: H
authors.lastname: Li
authors.forename: Yongbai
authors.initials: Y
authors.lastname: Luo
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D051242:Caveolin 1 / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D054855:Drug-Eluting Stents; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D005434:Flow Cytometry; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D051242:Caveolin 1; D007166:Immunosuppressive Agents; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D003474:Curcumin; D020123:Sirolimus