Role of hypoxia inducible factor-1伪 in remote limb ischemic preconditioning
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- 作者：Hussein Kalakech ; Sophie Tamareille ; S ; rine Pons ; Diane Godin-Ribuot ; Peter Carmeliet ; Alain Furber ; Val茅rie Martin ; Alain Berdeaux ; Bijan Ghaleh ; Fabrice Prunier
- 关键词：RIPC ; remote ischemic preconditioning ; I/R ; ischemia/reperfusion ; HIF-1伪 ; hypoxia inducible factor-1伪 ; HIF1a ; gene encoding the HIF-1伪 protein ; MI ; myocardial infarction ; Cd ; cadmium ; IS ; infarct size ; IPC ; local ischemic preconditioning ; PCR ; polymerase chain reaction ; AAR ; area at risk ; TTC ; triphenyltetrazolium chloride ; P-GSK-3尾 ; phospho-Glycogen Synthase Kinase-3尾 ; GSK-3尾 ; total GSK-3尾 ; GAPDH ; glyceraldehyde 3-phosphate dehydrogenase ; SEM ; standard error of the mean ; siRNA ; small int
- 刊名：Journal of Molecular and Cellular Cardiology
- 出版年：December, 2013
- 年：2013
- 卷：65
- 期：Complete
- 页码：98-104
- 全文大小：581 K
文摘
Remote ischemic preconditioning (RIPC) has emerged as a feasible and attractive therapeutic procedure for heart protection against ischemia/reperfusion (I/R) injury. However, its molecular mechanisms remain poorly understood. Hypoxia inducible factor-1伪 (HIF-1伪) is a transcription factor that plays a key role in the cellular adaptation to hypoxia and ischemia. This study's aim was to test whether RIPC-induced cardioprotection requires HIF-1伪 upregulation to be effective. In the first study, wild-type mice and mice heterozygous for HIF1a (gene encoding the HIF-1伪 protein) were subjected to RIPC immediately before myocardial infarction (MI). RIPC resulted in a robust HIF-1伪 activation in the limb and acute cardioprotection in wild-type mice. RIPC-induced cardioprotection was preserved in heterozygous mice, despite the low HIF-1伪 expression in their limbs. In the second study, the role of HIF-1伪 in RIPC was evaluated using cadmium (Cd), a pharmacological HIF-1伪 inhibitor. Rats were subjected to MI (MI group) or to RIPC immediately prior to MI (R-MI group). Cd was injected 180 min before RIPC (Cd-R-MI group). RIPC induced robust HIF-1伪 activation in rat limbs and significantly reduced infarct size (IS). Despite Cd's inhibition of HIF-1伪 activation, RIPC-induced cardioprotection was preserved in the Cd-R-MI group. RIPC applied immediately prior to MI increased HIF-1伪 expression and attenuated IS in rats and wild-type mice. However, RIPC-induced cardioprotection was preserved in partially HIF1a-deficient mice and in rats pretreated with Cd. When considered together, these results suggest that HIF-1伪 upregulation is unnecessary in acute RIPC.