Department of Cardiology, Medical School of Jinan University, Guangzhou, China.
Arch Med Res. 2009 Oct;40(7):605-11. doi: 10.1016/j.arcmed.2009.09.001.
Elevated activities of matrix metalloproteinases (MMPs) following acute myocardial infarction (AMI) have been shown to mediate ventricular remodeling. The extracellular MMP inducer (EMMPRIN) plays a key regulatory role for MMP activities. The aim of this study was to evaluate changes of EMMPRIN, MMP-2 and MMP-9 and determine the correlation between EMMPRIN expression and MMPs in human left ventricle after AMI.
Immunohistochemistry for MMP-2, MMP-9 and EMMPRIN were performed postmortem in 15 human left ventricles including 10 patients with AMI and five normal subjects who were accident victims. Western blot was used to determine protein levels of MMP-2, MMP-9 and EMMPRIN. The correlation between EMMPRIN expression and MMPs was determined by linear regression.
Our results showed that there was slight EMMPRIN expression on the membranes of normal cardiac myocytes, whereas its expression strongly increased around the zone of necrosis in the AMI group. Compared with the control group, EMMPRIN (1.10+/-0.17 vs. 0.25+/-0.04, p<0.001), MMP-2 (0.25+/-0.03 vs. 0.64+/-0.11, p<0.001) and MMP-9 (0.16+/-0.03 vs. 0.39+/-0.07, p<0.001) protein levels were significantly increased in the AMI group. The expression of MMP-2 (r(2)=0.82, p<0.001), and MMP-9 (r(2)=0.424, p=0.041) were correlated with EMMPRIN expression in AMI patients.
Our findings demonstrate for the first time that EMMPRIN expression increases in the human left ventricle after AMI. As one of the upregulators of local MMP expression, augmented expression of EMMPRIN may play a critical role in ventricular remodeling in AMI subjects.
研究表明,急性心肌梗死(AMI)后基质金属蛋白酶(MMPs)活性升高介导心室重构。细胞外基质金属蛋白酶诱导因子(EMMPRIN)对 MMP 活性起着关键的调节作用。本研究旨在评估 AMI 后人类左心室中 EMMPRIN、MMP-2 和 MMP-9 的变化,并确定 EMMPRIN 表达与 MMPs 之间的相关性。
对包括 10 例 AMI 患者和 5 例意外死亡的正常对照组共 15 例人类左心室进行 MMP-2、MMP-9 和 EMMPRIN 的免疫组化染色。采用 Western blot 法测定 MMP-2、MMP-9 和 EMMPRIN 的蛋白水平。采用线性回归法确定 EMMPRIN 表达与 MMPs 之间的相关性。
结果显示,正常心肌细胞的细胞膜上有轻微的 EMMPRIN 表达,而在 AMI 组的坏死区周围其表达明显增强。与对照组相比,AMI 组的 EMMPRIN(1.10+/-0.17 比 0.25+/-0.04,p<0.001)、MMP-2(0.25+/-0.03 比 0.64+/-0.11,p<0.001)和 MMP-9(0.16+/-0.03 比 0.39+/-0.07,p<0.001)蛋白水平均显著增加。在 AMI 患者中,MMP-2(r(2)=0.82,p<0.001)和 MMP-9(r(2)=0.424,p=0.041)的表达与 EMMPRIN 的表达呈正相关。
本研究首次证明,EMMPRIN 在 AMI 后人类左心室中的表达增加。作为局部 MMP 表达的上调因子之一,EMMPRIN 的表达增加可能在 AMI 患者的心室重构中发挥关键作用。