Myocardial and interstitial matrix metalloproteinase activity after acute myocardial infarction in pigs
Myocardial and interstitial matrix metalloproteinase activity after acute myocardial infarction in pigs
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DOI：
10.1152/ajpheart.2001.281.3.h987
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发表时间：
2001-09-01
影响因子：
4.8
通讯作者：
Spinale, FG
中科院分区：
文献类型：
--
作者：
Etoh, T;Joffs, C;Spinale, FG
心肌梗死（MI）演变过程中的一个结构事件是左心室（LV）重构。导致MI后LV心肌重塑早期变化的机制仍知之甚少。基质金属蛋白酶（MMP）有助于在几种疾病状态下的组织重塑。急性心肌梗死后，MMP是否以及在何种程度上激活发生在心肌内膜仍有待确定。成年猪（n = 15）的仪器，以测量区域内的回旋支和左前降支动脉的心肌功能和间质MMP水平。区域功能测定声显微镜，并通过选择性微透析和酶谱以及MMP间质荧光活性测定间质MMP水平。在基线和结扎旋动脉钝缘后3小时内连续进行测量。冠状动脉闭塞后，MI区域的局部短缩分数下降超过50%，但远端区域保持不变。心肌间质样品的酶谱活性显示，可溶性基质金属蛋白酶的释放增加2小时后MI。MI后酶谱活性增加与MMP-9一致。心肌间质基质金属蛋白酶荧光活性成为检测缺血区域内早在10分钟后冠状动脉闭塞和显着增加后1小时MI。MMP荧光活性与偏远地区的基线值相比保持不变。目前的研究表明，心肌MMP激活可以发生在MI区域内，在没有再灌注。这些独特的结果表明，MMP的释放和激活发生在心肌梗死后早期的缺血心肌细胞内。
A structural event during the evolution of a myocardial infarction (MI) is left ventricular (LV) remodeling. The mechanisms that contribute to early changes in LV myocardial remodeling in the post-MI period remain poorly understood. Matrix metalloproteinases (MMPs) contribute to tissue remodeling in several disease states. Whether and to what degree MMP activation occurs within the myocardial interstitium after acute MI remains to be determined. Adult pigs (n = 15) were instrumented to measure regional myocardial function and interstitial MMP levels within regions served by the circumflex and left anterior descending arteries. Regional function was measured by sonomicrometry, and interstitial MMP levels were determined by selective microdialysis and zymography as well as by MMP interstitial fluorogenic activity. Measurements were performed at baseline and sequentially for up to 3 h after ligation of the obtuse marginals of the circumflex artery. Regional fractional shortening fell by over 50% in the MI region but remained unchanged in the remote region after coronary occlusion. Release of soluble MMPs, as revealed by zymographic activity of myocardial interstitial samples, increased by 2 h post-MI. The increased zymographic activity after MI was consistent with MMP-9. Myocardial interstitial MMP fluorogenic activity became detectable within the ischemic region as early as 10 min after coronary occlusion and significantly increased after 1 h post-MI. MMP fluorogenic activity remained unchanged from baseline values in the remote region. The present study demonstrated that myocardial MMP activation can occur within the MI region in the absence of reperfusion. These unique results suggest that MMP release and activation occurs within the ischemic myocardial interstitium in the early post-MI period.