Copper depletion is associated with myocardial ischemic infarction, in which copper metabolism MURR domain 1 (COMMD1) is increased. The present study was undertaken to test the hypothesis that the elevated COMMD1 is responsible for copper loss from the ischemic myocardium, thus worsening myocardial ischemic injury. Mice (C57BL/6J) were subjected to left anterior descending coronary artery permanent ligation to induce myocardial ischemic infarction. In the ischemic myocardium, copper reduction was associated with a significant increase in the protein level of COMMD1. A tamoxifen-inducible, cardiomyocyte -specific Commd1 knockout mouse (C57BL/6J) model (COMMD1^CMC▲/▲) was generated using the Cre-LoxP recombination system. COMMD1^CMC▲/▲ and wild-type littermates were subjected to the same permanent ligation of left anterior descending coronary artery. At the 7th day after ischemic insult, COMMD1 deficiency suppressed copper loss in the heart, along with preservation of vascular endothelial growth factor and vascular endothelial growth factor receptor 1 expression and the integrity of the vascular system in the ischemic myocardium. Corresponding to this change, infarct size of ischemic heart was reduced and myocardial contractile function was well preserved in COMMD1^CMC▲/▲ mice. These results thus demonstrate that upregulation of COMMD1 is at least partially responsible for copper efflux from the ischemic heart. Cardiomyocyte-specific deletion of COMMD1 helps preserve the availability of copper for angiogenesis, thus suppressing myocardial ischemic dysfunction.

铜耗竭与心肌缺血性梗死相关，其中铜代谢 MURR 结构域 1 (COMMD1) 增加。本研究旨在检验 COMMD1 升高是造成缺血性心肌铜流失，从而加重心肌缺血性损伤的假设。对小鼠（C57BL/6J）进行左冠状动脉前降支永久结扎以诱导心肌缺血性梗死。在缺血性心肌中，铜还原与 COMMD1 蛋白水平的显着增加有关。使用Cre-LoxP重组系统生成了他莫昔芬诱导型心肌细胞特异性Commd1敲除小鼠 (C57BL/6J) 模型 ( COMMD1 ^CMC▲/▲ ) 。COMMD1^CMC▲/▲与野生型同窝仔猪进行相同的左冠状动脉前降支永久结扎。在缺血性损伤后第 7 天，COMMD1 缺乏抑制了心脏中的铜流失，同时保留了血管内皮生长因子和血管内皮生长因子受体 1 的表达以及缺血心肌中血管系统的完整性。与这种变化相对应的是， COMMD1 CMC中缺血性心脏的梗塞面积减小，心肌收缩功能得到很好的保留^▲/▲老鼠。因此，这些结果表明，COMMD1 的上调至少部分负责缺血性心脏的铜流出。COMMD1 的心肌细胞特异性缺失有助于保持铜对血管生成的可用性，从而抑制心肌缺血功能障碍。