Original ArticleCurcumin Attenuates Rapamycin-induced Cell Injury of Vascular Endothelial CellsGuo, Ning MD; Chen, Fangyuan PhD; Zhou, Juan PhD; Fang, Yuan MD; Li, Hongbing MD; Luo, Yongbai MD; Zhang, Yong MDAuthor Information Department of Cardiology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China. Reprints: Ning Guo, MD, Department of Cardiology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 277 Yanta West Road, Xi'an 710061, China (e-mail: [email protected]). Supported by grants from the National Natural Science Foundation of China (No. 81170138). The authors report no conflicts of interest. Received December 28, 2014 Accepted May 09, 2015 Journal of Cardiovascular Pharmacology: October 2015 - Volume 66 - Issue 4 - p 338-346 doi: 10.1097/FJC.0000000000000285 Buy Metrics 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. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.