Hypoxia-inducible factor 1 is required for remote ischemic preconditioning of the heart

Cai Z.; Luo W.; Zhan H.Semenza G.L.

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Hypoxia-inducible factor 1 is required for remote ischemic preconditioning of the heart

机译：Hypoxia-inducible factor 1 is required for remote ischemic preconditioning of the heart

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Both preclinical and clinical studies suggest that brief cycles of ischemia and reperfusion in the arm or leg may protect the heart against injury following prolonged coronary artery occlusion and reperfusion, a phenomenon known as remote ischemic preconditioning. Recent studies in mice indicate that increased plasma interleukin-10 (IL-10) levels play an important role in remote ischemic preconditioning induced by clamping the femoral artery for 5 min followed by 5 min of reperfusion for a total of three cycles. In this study, we demonstrate that remote ischemic preconditioning increases plasma IL-10 levels and decreases myocardial infarct size in wild-type mice but not in littermates that are heterozygous for a knockout allele at the locus encoding hypoxia-inducible factor (HIF) 1α. Injection of a recombinant adenovirus encoding a constitutively active form of HIF-1α into mouse hind limb muscle was sufficient to increase plasma IL-10 levels and decrease myocardial infarct size. Exposure of C2C12 mouse myocytes to cyclic hypoxia and reoxygenation rapidly increased levels of IL-10 mRNA, which was blocked by administration of the HIF-1 inhibitor acriflavine or by expression of short hairpin RNA targeting HIF-1α or HIF-1β. Chromatin immunoprecipitation assays demonstrated that binding of HIF-1 to the Il10 gene was induced when myocytes were subjected to cyclic hypoxia and reoxygenation. Taken together, these data indicate that HIF-1 activates Il10 gene transcription and is required for remote ischemic preconditioning.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第43期|17462-17467|共6页
作者
Cai Z.; Luo W.; Zhan H.Semenza G.L.;
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作者单位

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States;

Department of Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Cardiac surgery; Cardioprotection; Coronary heart disease; Myocardial infarction;

Hypoxia-inducible factor 1 is required for remote ischemic preconditioning of the heart

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