Activation of mitogen-activated protein kinases in the non-ischemic myocardium of an acute myocardial infarction in rats.

K. Yoshida, M. Yoshiyama, T. Omura, Y. Nakamura, S. Kim, K. Takeuchi, H. Iwao, J. Yoshikawa
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引用次数: 22

Abstract

As one of the signal transduction pathways related to myocardial remodeling, mitogen-activated protein kinases (MAPKs) possibly play an important role in ischemic heart disease, but it is still unknown whether myocardial MAPKs are activated in the non-ischemic region of an acute myocardial infarction (AMI). Therefore, the present study investigated the myocardial activity of extracellular signal-regulated kinases (ERKs), c-Jun NH2 terminal kinases (JNKs) and p38MAPK during the acute phase of an infarction of the rat heart, and measured the geometrical ventricular changes by echocardiography. All MAPKs were significantly activated in the ischemic myocardium (IM), non-ischemic septal wall (SW), and right ventricular wall (RV). Furthermore, the activation patterns of MAPKs differed in each region. The activation of p44ERK, JNKs and p38MAPK in the IM occurred rapidly after myocardial ischemia, followed by those in the SW and RV. The activator protein-1 DNA binding activities of the IM, SW and RV increased significantly at I day after coronary ligation. Echocardiography showed increased SW motion and RV dilatation. In conclusion, this is the first in vivo evidence that myocardial MAPKs are activated in the non-ischemic region of an AMI. Echocardiographic results suggest that acceleration of workload and/or stretch may partially induce the activation of MAPKs.
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大鼠急性心肌梗死非缺血心肌中丝裂原活化蛋白激酶的激活。
作为与心肌重构相关的信号转导途径之一,丝裂原活化蛋白激酶(MAPKs)可能在缺血性心脏病中发挥重要作用,但心肌MAPKs是否在急性心肌梗死(AMI)的非缺血区被激活尚不清楚。因此,本研究研究了大鼠心肌梗死急性期细胞外信号调节激酶(ERKs)、c-Jun NH2末端激酶(JNKs)和p38MAPK的心肌活性,并通过超声心动图测量心室几何变化。所有MAPKs在缺血心肌(IM)、非缺血性室间隔壁(SW)和右心室壁(RV)中均被显著激活。此外,每个区域的mapk激活模式不同。心肌缺血后,IM中p44ERK、JNKs和p38MAPK的激活迅速发生,其次是SW和RV。冠脉结扎后第1天,IM、SW和RV的激活蛋白-1 DNA结合活性显著升高。超声心动图显示左室运动增强,右室扩张。总之,这是第一个在体内证明心肌MAPKs在AMI的非缺血区域被激活的证据。超声心动图结果表明,加速工作负荷和/或拉伸可能部分诱导MAPKs的激活。
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