The proton-gated acid-sensing ion channel 1a (ASIC1a) is implicated in the injury responseto cerebral ischemia but little is known about its role in cardiac ischemia. We provide genetic evidence that ASIC1a is involved in myocardial ischemia-reperfusion injury (IRI) and show that pharmacological inhibition of ASIC1a yields robust cardioprotection in rodent and human models of cardiac ischemia, resulting in improved post-IRI cardiac viability and function. Consistent with a key role for ASIC1a in cardiac ischemia, we show that polymorphisms in the ASIC1 genetic locus are strongly associated with myocardial infarction. Collectively, our data provide compelling evidence that ASIC1a is a key target for cardioprotective drugs to reduce the burden of disease associated with myocardial ischemia.

中文翻译：

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酸敏感离子通道1a是心脏缺血再灌注损伤的关键介质

质子门控酸敏感离子通道1a（ASIC1a）参与了对脑缺血的损伤反应，但对其在心脏缺血中的作用知之甚少。我们提供了遗传学证据，表明ASIC1a参与了心肌缺血再灌注损伤（IRI），并表明在啮齿动物和人类心脏缺血模型中，ASIC1a的药理抑制作用产生了强大的心脏保护作用，从而改善了IRI后的心脏生存能力和功能。与ASIC1a在心脏缺血中的关键作用一致，我们表明ASIC1遗传基因座中的多态性与心肌梗塞密切相关。总的来说，我们的数据提供了令人信服的证据，表明ASIC1a是心脏保护药物减少与心肌缺血相关的疾病负担的关键靶标。