CaMKII inhibition reduces isoproterenol-induced ischemia and arrhythmias in hypertrophic mice.
CaMKII inhibition reduces isoproterenol-induced ischemia and arrhythmias in hypertrophic mice.
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DOI：
10.18632/oncotarget.15099
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发表时间：
2017-03-14
期刊：
影响因子：
--
通讯作者：
Wang Y
中科院分区：
文献类型：
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作者：
Feng Y;Cheng J;Wei B;Wang Y
Ca/钙调蛋白依赖性蛋白激酶 II (CaMKII) 是一种致心律失常分子，在心脏肥大时过度激活。在这里，我们研究了 CaMKII 抑制对异丙肾上腺素 (ISO) 诱导的肥大小鼠心律失常的影响。 ISO 在肥大小鼠中诱导多种类型的心律失常，但在正常小鼠中则不然。在心律失常开始之前，ISO 使 QTc 间期延长，T 波振幅显着增加。 CaMKII 的抑制可防止 ISO 诱导的 QTc 延长和 T 波抬高，并消除心律失常诱导。通过胸主动脉束带诱导小鼠压力超负荷心脏肥大。通过心电图记录清醒小鼠的心律失常。 CaMKII抑制可有效抑制心脏肥大中肾上腺素能激活诱发的室性心律失常，其中心室缺血诱发的CaMKII激活发挥重要作用。
The Ca/calmodulin-dependent protein kinase II (CaMKII), an arrhythmogenic molecule, is excessively activated in cardiac hypertrophy. Here, we investigated the effect of CaMKII inhibition in isoproterenol (ISO)-induced arrhythmias in hypertrophic mice. ISO induced multiple types of arrhythmias in the hypertrophic mice but not in the normal mice. The QTc intervals were prolonged and the amplitudes of T waves were increased significantly by ISO prior to arrhythmia initiation. Inhibition of CaMKII prevented ISO-induced QTc prolongation and T wave elevation and abrogated arrhythmia induction. Pressure-overload cardiac hypertrophy was induced in mice by thoracic aortic banding. Arrhythmias were recorded by electrocardiogram in conscious mice. CaMKII inhibition is effective in suppressing adrenergic activation-induced ventricular arrhythmias in cardiac hypertrophy, of which the ventricular ischemia-induced CaMKII activation plays an important role.