Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8474973 | Journal of Molecular and Cellular Cardiology | 2013 | 7 Pages |
Abstract
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-1α (HIF-1α) 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-1α upregulation to be effective. In the first study, wild-type mice and mice heterozygous for HIF1a (gene encoding the HIF-1α protein) were subjected to RIPC immediately before myocardial infarction (MI). RIPC resulted in a robust HIF-1α activation in the limb and acute cardioprotection in wild-type mice. RIPC-induced cardioprotection was preserved in heterozygous mice, despite the low HIF-1α expression in their limbs. In the second study, the role of HIF-1α in RIPC was evaluated using cadmium (Cd), a pharmacological HIF-1α 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-1α activation in rat limbs and significantly reduced infarct size (IS). Despite Cd's inhibition of HIF-1α activation, RIPC-induced cardioprotection was preserved in the Cd-R-MI group. RIPC applied immediately prior to MI increased HIF-1α 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-1α upregulation is unnecessary in acute RIPC.
Keywords
GSK-3βp-GSK-3βRIPCIPCHIF-1αNF-κBTTCAARGAPDHDNAHIF1aI/RSmall interfering RNAsiRNAIschemia/reperfusion injuryMyocardial infarctiondeoxyribonucleic acidInfarct sizeischemia/reperfusionTriphenyltetrazolium chloridestandard error of the meanhypoxia inducible factor-1αVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)Nuclear factor-kappa Bphosphatase and tensin homologphospho-glycogen synthase kinase-3βSEMarea at riskpolymerase chain reactionPCRRemote ischemic preconditioningPtenCadmiumglyceraldehyde 3-phosphate dehydrogenase
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Authors
Hussein Kalakech, Sophie Tamareille, Sandrine Pons, Diane Godin-Ribuot, Peter Carmeliet, Alain Furber, Valérie Martin, Alain Berdeaux, Bijan Ghaleh, Fabrice Prunier,