title: Mechanism of uncoupling protein 2‑mediated myocardial injury in hypothermic preserved rat hearts.
abstract: In the present study, the alterations in uncoupling protein 2 (UCP2) expression following hypothermic preservation in rat hearts were investigated. Isolated rat hearts were preserved in Celsior solution for 3‑12 h followed by 60 min of reperfusion. The cardiac function was evaluated using the Langendorff perfusion system. UCP2 and silent mating type information regulation 2 homolog 1 (SIRT1) proteins were detected by western blot analysis. The ATP production and mitochondrial reactive oxygen species (ROS) levels were assessed. Subsequent to preservation in ice‑cold Celsior solution for 3‑12 h, the UCP2 protein expression in rat hearts was observed to increase in a time‑dependent manner. The UCP2 inhibitor genipin inhibited the hypothermic preservation‑induced cardiac dysfunction, prevented a decline in ATP production induced by 9 h of preservation, however had no effect on the hypothermic preservation‑induced increase in mitochondrial ROS levels. Compared with the control group, the SIRT1 protein expression in rat hearts reduced following hypothermic preservation. Compared with the 9‑h preservation group, Celsior solution supplemented with the SIRT1 activator resveratrol (20 or 40 µmol/l) inhibited UCP2 protein overexpression, prevented the decline in ATP production and resulted in an improvement cardiac function. The SIRT1 inhibitor EX‑527 abolished the resveratrol‑induced inhibition of UCP2 overexpression and cardiac protection in the hypothermic preserved rat heart. These observations suggest that downregulation of UCP2 expression in the hypothermic preserved rat heart in part initiated the protective mechanism via the SIRT1 pathway.
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Gai-Ge
authors.initials: GG
authors.lastname: Chen
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Jin-Bin
authors.initials: JB
authors.lastname: Yan
authors.affiliation: Department of Pharmacology, Medicine School, Taizhou University, Taizhou, Zhejiang 317000, P.R. China.
authors.forename: Xu-Ming
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Zhejiang Medical College, Hangzhou, Zhejiang 310053, P.R. China.
authors.forename: Ming-Zhi
authors.initials: MZ
authors.lastname: Zheng
authors.affiliation: Department of Clinical Medicine, Zhejiang Medical College, Hangzhou, Zhejiang 310053, P.R. China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Jiang
authors.affiliation: Department of Physiology, Jiaxing University College of Medicine, Jiaxing, Zhejiang 314001, P.R. China.
authors.forename: Xin-Mei
authors.initials: XM
authors.lastname: Zhou
authors.affiliation: Department of Medical Affairs, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Cai
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Yue-Liang
authors.initials: YL
authors.lastname: Shen
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D015925:Cryopreservation; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D009926:Organ Preservation / Q000009:adverse effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology; D000071246:Uncoupling Protein 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: C550547:6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide; D000975:Antioxidants; D002227:Carbazoles; D017382:Reactive Oxygen Species; D013267:Stilbenes; D000071246:Uncoupling Protein 2; D000255:Adenosine Triphosphate; D056564:Sirtuin 1; D000077185:Resveratrol