Transient Receptor Potential Ankyrin 1 Activation within the Cardiac Myocyte Limits Ischemia-reperfusion Injury in Rodents.
Transient Receptor Potential Ankyrin 1 Activation within the Cardiac Myocyte Limits Ischemia-reperfusion Injury in Rodents.
复制标题
啮齿动物中心肌细胞限制缺血 - 再灌注损伤内的瞬态受体势伸蛋白1激活。
DOI：
10.1097/aln.0000000000001377
复制
发表时间：
2016-12
期刊：
影响因子：
8.8
通讯作者：
Gross ER
中科院分区：
文献类型：
--
作者：
Lu Y;Piplani H;McAllister SL;Hurt CM;Gross ER
最近的证据表明，在疼痛信号传导和缺血再灌注损伤的重要细胞通路之间存在串扰。在这里，我们解决是否瞬时受体电位锚蛋白1（TRPA 1）通道，疼痛信号的重要性，是目前在心肌细胞和调节心脏缺血再灌注损伤。对于TRPA 1的生化分析，使用包括qPCR、蛋白质印迹和免疫荧光的技术。为了确定TRPA 1是如何介导细胞损伤的，我们使用了大鼠心脏缺血-再灌注损伤的体内模型和成年大鼠分离的心肌细胞进行缺氧-复氧。我们的生化分析表明TRPA 1位于心肌细胞内。此外，使用心脏损伤的大鼠体内模型，TRPA 1激活剂ASP 7663和optovin减少心肌损伤（分别为45±5%*，44±8%*，相对于对照组66±6%的梗死面积/风险面积，n=6/组，平均值±SD，*P<0.001）。TRPA 1抑制也阻断了吗啡的梗死面积保留作用。在分离的心肌细胞中，当在复氧期间给予TRPA 1激活剂ASP 7663和optovin时，减少心肌细胞死亡（20±3%*，22±4%*，对比36± 3%，每个视野的死亡细胞%，n=6/组，平均值±SD，*P<0.05）。对于心脏损伤的大鼠体内模型，TRPA 1激活剂的梗死面积保留效应也发生在再灌注期间。我们的数据表明，TRPA 1存在于心肌细胞内，并在调节心肌再灌注损伤中起重要作用。心肌细胞中TRPA 1的存在可能解释了为什么某些可以阻断TRPA 1激活的止痛药，如环氧合酶-2（考克斯-2）抑制剂或一些非甾体抗炎药（NSAID）可能与心血管风险相关。
Recent evidence suggests cross-talk exists between cellular pathways important for pain signaling and ischemia-reperfusion injury. Here we address whether the transient receptor potential ankyrin 1 (TRPA1) channel, important in pain signaling, is present in cardiac myocytes and regulates cardiac ischemia-reperfusion injury. For biochemical analysis of TRPA1, techniques including qPCR, western blot, and immunofluorescence were used. To determine how TRPA1 mediates cellular injury, we used an in vivo model of rat cardiac ischemia-reperfusion injury and adult rat isolated cardiac myocytes subjected to hypoxia-reoxygenation. Our biochemical analysis indicates TRPA1 is within the cardiac myocytes. Further, using a rat in vivo model of cardiac injury, the TRPA1 activators ASP7663 and optovin reduce myocardial injury (45±5%*, 44±8%*, respectively, versus control 66±6% infarct size/area at risk, n=6/group, mean±SD, *P<0.001). TRPA1 inhibition also blocked the infarct size sparing effects of morphine. In isolated cardiac myocytes, the TRPA1 activators ASP7663 and optovin reduce cardiac myocyte cell death when given during reoxygenation (20±3%*, 22±4%*, versus 36±3%, % of dead cells per field, n=6/group, mean±SD, *P<0.05). For a rat in vivo model of cardiac injury, the infarct size sparing effect of TRPA1 activators also occurs during reperfusion. Our data suggests that TRPA1 is present within the cardiac myocytes and is important in regulating myocardial reperfusion injury. The presence of TRPA1 within the cardiac myocytes may potentially explain why certain pain relievers that can block TRPA1 activation, such as cyclooxygenase-2 (COX-2) inhibitors or some non-steroidal anti-inflammatory drugs (NSAIDs), could be associated with cardiovascular risk.