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本公众号每天分享一篇最新一期Anesthesia & Analgesia等SCI杂志的摘要翻译，敬请关注并提出宝贵意见 Hypoxia-inducible factor 2-alpha-dependent induction of amphiregulin dampens myocardial ischemia-reperfusion injury 背景与目的 心肌缺血-再灌注损伤（IRI）时，低氧诱导因子α-1（HIFα-1）和低氧诱导因子α-2（HIFa-2）等转录因子可稳定地表达。有研究表明HIFα-1具有心脏保护作用，但HIFα-2是否有相同的作用尚不清楚。 方 法 本研究发现HIFα-2可诱导上皮生长因子双调蛋白（AREG）对心肌IRI产生心肌保护作用。比较缺失HIFα-1或HIFα-2的小鼠心肌细胞，发现HIFα-2的缺失心肌细胞梗死面积增加。对传代培养或培养的人原代心肌细胞进行微阵列研究，发现 HIFα-2可诱导心肌中AREG的表达，同样，AREG在缺血性心脏病患者的心肌组织中表达增加。 结 果 AREG缺乏可增加心肌IRI，对AREG信号通路进行药物抑制作用也如此。相反，用重组AREG处理并重建了HIFα-2缺失的小鼠心肌细胞可产生心肌保护作用。 结 论 本研究表明HIFα-2可诱导心肌细胞中AREG的表达，这增加了心肌缺血的耐受性 原始文献摘要 Koeppen M, Lee J W, Seo S W, et al. Hypoxia-inducible factor 2-alpha-dependent induction of amphiregulin dampens myocardial ischemia-reperfusion injury.[J]. Nature Communications, 2018, 9(1):816. Abstract:Myocardial ischemia-reperfusion injury (IRI) leads to the stabilization of the transcription factors hypoxia-inducible factor 1-alpha (HIF1-alpha) and hypoxia-inducible factor 2-alpha (HIF2-alpha). While previous studies implicate HIF1-alpha in cardioprotection, the role of HIF2-alpha remains elusive. Here we show that HIF2-alpha induces the epithelial growth factor amphiregulin (AREG) to elicit cardioprotection in myocardial IRI. Comparing mice with inducible deletion of Hif1a or Hif2a in cardiac myocytes, we show that loss of Hif2-alpha increases infarct sizes. Microarray studies in genetic models or cultured human cardiac myocytes implicate HIF2-alpha in the myocardial induction of AREG. Likewise, AREG increases in myocardial tissues from patients with ischemic heart disease. Areg deficiency increases myocardial IRI, as does pharmacologic inhibition of Areg signaling. In contrast, treatment with recombinant Areg provides cardioprotection and reconstitutes mice with Hif2a deletion. These studies indicate that HIF2-alpha induces myocardial AREG expression in cardiac myocytes, which increases myocardial ischemia tolerance. 麻醉学文献进展分享 联系我们 |
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