title: Delayed reendothelialization with rapamycin is rescued by the addition of nicorandil in balloon-injured rat carotid arteries.
abstract: Rapamycin is an immunosuppressive agent that is added to drug eluting stents. It prevents restenosis, but it also impairs reendothelialization. Nicorandil is a hybrid agent with adenosine triphosphated (ATP)-sensitive K+ (KATP) channel opener and nitrate properties. It prevents oxidative stress and cell apoptosis induced by rapamycin in endothelial cells in vitro. However, whether nicorandil promotes reendothelialization after angioplasty delayed by rapamycin remains to be determined. Balloon injury model was established in SD rats. Nicorandil increased reendothelialization impaired by rapamycin, and it decreased xanthine oxidase (XO)-generated reactive oxygen species (ROS) induced by rapamycin. In addition, eNOS expression inhibited by rapamycin was increased by nicorandil in vivo. In vitro, rapamycin-impeded cardiac microvascular endothelial cells (CMECs) migration, proliferation and rapamycin-induced ROS production were reversed by nicorandil. Knockdown of XO partially inhibited rapamycin-induced ROS production and cell apoptosis in CMECs, and it promoted CMECs migration and proliferation suppressed by rapamycin. Knockdown of Akt partially prevents eNOS upregulation promoted by nicorandil. The beneficial effect of nicorandil is exhibited by inhibiting XO and up-regulating Akt pathway. Nicorandil combined with rapamycin in effect rescue the deficiencies of rapamycin alone in arterial healing after angioplasty.
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Ying Qian
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Tian
authors.affiliation: Department of Cardiology, Chinese PLA 175th Hospital, Fujian, China.|Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Jin Song
authors.initials: JS
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yun Dai
authors.initials: YD
authors.lastname: Chen
authors.affiliation: VIP Medical Service Department, Beijing Shijitan Hospital, Beijing, China.|Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020212:Carotid Artery Injuries / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects*; D020108:Nicorandil / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D020108:Nicorandil; D052250:Nitric Oxide Synthase Type III; D014969:Xanthine Oxidase; D051057:Proto-Oncogene Proteins c-akt; D020123:Sirolimus
keywords: angioplasty; endothelium; nicorandil; rapamycin; xanthine oxidase