Role of hypoxia inducible factor-1α in remote limb ischemic preconditioning.
J Mol Cell Cardiol
; 65: 98-104, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-24140799
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 18 0min 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.
Palavras-chave
AAR; Cd; DNA; GAPDH; GSK-3ß; HIF-1α; HIF1a; Hypoxia inducible factor-1α; I/R; IPC; IS; Ischemia/reperfusion injury; MI; NF-κB; P-GSK-3ß; PCR; PTEN; RIPC; Remote ischemic preconditioning; SEM; TTC; VEGF; area at risk; cadmium; deoxyribonucleic acid; gene encoding the HIF-1α protein; glyceraldehyde 3-phosphate dehydrogenase; hypoxia inducible factor-1α; infarct size; ischemia/reperfusion; local ischemic preconditioning; myocardial infarction; nuclear factor-kappa B; phosphatase and tensin homolog; phospho-Glycogen Synthase Kinase-3ß; polymerase chain reaction; remote ischemic preconditioning; siRNA; small interfering RNA; standard error of the mean; total GSK-3ß; triphenyltetrazolium chloride; vascular endothelial growth factor
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Precondicionamento Isquêmico
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Subunidade alfa do Fator 1 Induzível por Hipóxia
/
Extremidades
Limite:
Animals
Idioma:
En
Revista:
J Mol Cell Cardiol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
França