Temporal changes in matrix metalloproteinase expression and inflammatory response associated with cardiac rupture after myocardial infarction in mice
Temporal changes in matrix metalloproteinase expression and inflammatory response associated with cardiac rupture after myocardial infarction in mice
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DOI：
10.1016/j.lfs.2003.09.042
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发表时间：
2004-02-06
期刊：
影响因子：
6.1
通讯作者：
Yang, XP
中科院分区：
文献类型：
--
作者：
Tao, ZY;Cavasin, MA;Yang, XP
我们先前发现，患有心肌梗死(MI)的雄性小鼠心脏破裂的发生率很高，通常发生在MI后3至5天。鉴于基质金属蛋白酶(MMPs)在心肌梗死后心肌梗死愈合、组织修复和细胞外基质(ECM)重建中的重要作用，我们研究了急性心肌梗死后心脏破裂时基质金属蛋白酶表达与炎症反应的时间关系。雄性C57BL/6J小鼠结扎冠状动脉左前降支造成心肌梗死，分别于心肌梗死后1、2、4、7、14天处死。酶谱法检测心脏组织中基质金属蛋白酶-2和基质金属蛋白酶-9活性。羟脯氨酸法测定胶原含量。我们发现心肌梗死后1天，基质金属蛋白酶-9的活性就开始升高，2-4天达到最大，同时梗死区中性粒细胞和巨噬细胞的浸润也有类似的增加。MMP2在4d内开始迅速升高，7d达最大值，14d仍保持较高水平。巨噬细胞在心肌梗死后4天开始出现明显的巨噬细胞浸润，7~14天逐渐减少。胶原蛋白含量在心肌梗死后4天前没有变化，在此点上有所增加，此后保持在较高水平。我们的数据提示，在小鼠中，基质金属蛋白酶-2和基质金属蛋白酶-9的过度表达(可能主要由中性粒细胞和巨噬细胞表达)可能导致心肌梗死早期ECM过度降解，损害梗塞愈合，加重早期重塑，进而导致心脏破裂。(C)2003 Elsevier Inc.保留所有权利。
We previously found that male mice with myocardial infarction (MI) had a high rate of cardiac rupture, which generally occurred at 3 to 5 days after MI. Since matrix metalloproteinases (MMPs) play an important role in infarct healing, tissue repair and extracellular matrix (ECM) remodeling post-MI, we studied the temporal relationship of MMP expression and inflammatory response to cardiac rupture after acute MI. Male C57BL/6J mice were subjected to MI (induced by ligating the left anterior descending coronary artery) and killed 1, 2, 4, 7 or 14 days after MI. MMP-2 and MMP-9 activity in the heart were measured by zymography. Collagen content was measured by hydroxyproline assay. We found that after MI, MMP-9 activity increased as early as I day and reached a maximum by 2-4 days, associated with a similar increase in neutrophil and macrophage infiltration in the infarct area. MMP-2 started to increase rapidly within 4 days, reaching a maximum by 7 days and remaining high even at 14 days. Intense macrophage infiltration appeared by 4 days after MI and then gradually decreased within 7 to 14 days. Collagen content was unchanged until 4 days after MI, at which point it increased and remained high thereafter. Our data suggest that in mice, overexpression of MMP-2 and MMP-9 (possibly expressed mainly by neutrophils and macrophages) may lead to excessive ECM degradation in the early phase of MI, impairing infarct healing and aggravating early remodeling which in turn causes cardiac rupture. (C) 2003 Elsevier Inc. All rights reserved.