title: Hypercholesterolemia abrogates the protective effect of ischemic postconditioning by induction of apoptosis and impairment of activation of reperfusion injury salvage kinase pathway.
abstract: Ischemic postcontioning (IPoC) is an effective method to prevent myocardial ischemia reperfusion injury (MIRI), but its cardioprotection is usually blocked in the presence of hypercholesterolemia (HC) and the potential mechanism is still unknown. In this study, we investigated the roles of reperfusion injury salvage kinase (RISK) and apoptosis-related pathways in the attenuation of cardioprotection of IPoC in the presence of HC. The results showed that IPoC significantly decreased the infarct size and apoptosis, improved the recovery of ischemic myocardium, but these beneficial effects were reversed by high cholesterol diet-induced HC. Moreover, we also found that HC inhibited the phosphorylation of Akt and ERK1/2 which usually activated by IPoC in normal heart, induced excessive apoptosis by down-regulating Bcl-2 and up-regulating Bax, cytochrome c, caspase 9 and caspase 3 when compared with that in normal heart. Taken together, our results demonstrated that the cardioprotection of IPoC was abolished by HC, which was associated with inactivation of RISK signal pathway and dysregulation of downstream apoptosis-related pathway.
authors: Department of Cardiology, The First Affiliated Hospital of China Medical University, Liaoning, China.
authors: Nan
authors: N
authors: Wu
authors: Department of Medical Genetics, China Medical University, Liaoning, China.
authors: Xiaowen
authors: X
authors: Zhang
authors: Department of Clinical Medicine, China Medical University, Liaoning, China.
authors: Pengyu
authors: P
authors: Jia
authors: Department of Cardiology, The First Affiliated Hospital of China Medical University, Liaoning, China. Electronic address: jdl2001@126.com.
authors: Dalin
authors: D
authors: Jia
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D003331:Coronary Vessels; D045304:Cytochromes c / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D006937:Hypercholesterolemia / Q000378:metabolism* / Q000503:physiopathology*; D057775:Ischemic Postconditioning; D008055:Lipids / Q000097:blood; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017208:Rats, Wistar; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D008055:Lipids; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3; D053453:Caspase 9
keywords: Apoptosis; Hypercholesterolemia; Ischemia reperfusion injury; Ischemic postcoditioning; Reperfusion injury salvage kinase