Dynamic induction of ADAMTS1 gene in the early phase of acute myocardial infarction
Dynamic induction of ADAMTS1 gene in the early phase of acute myocardial infarction
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DOI：
10.1093/jb/mvh138
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发表时间：
2004-10-01
影响因子：
2.7
通讯作者：
Shiratori, Y
中科院分区：
文献类型：
--
作者：
Nakamura, K;Hirohata, S;Shiratori, Y
细胞外基质（ECM）降解酶如基质金属蛋白酶（MMPs）在梗死组织修复中发挥重要作用，影响心肌梗死后心室重构。ADAMTS1 （A disintegrin and metalloprotease with thrombospondin motif）是一种新发现的金属蛋白酶，最初是从癌细胞系中克隆出来的，但对其在疾病中的作用知之甚少。为了验证ADAMTS1在梗死心肌组织中出现的假设，我们通过Northern blotting、实时RT-PCR和原位杂交检测了ADAMTS1 mRNA在大鼠心肌梗死模型中的表达。正常内皮细胞表达少量ADAMTS1 mRNA，而正常心肌细胞不表达ADAMTS1 mRNA。冠状动脉结扎后3小时，Northern blot分析和实时RT-PCR证实ADAMTS1表达上调。原位杂交结果显示，心肌梗死后3 h，心肌内皮和心肌（主要在梗死区）表达强烈的ADAMTS1 mRNA信号。ADAMTS1基因在缺血心脏中的快速和短暂上调与其他MMPs的调节模式不同。我们的研究表明，ADAMTS1基因是在缺血内皮和心肌中表达的一个新的早期直接基因。
Extracellular matrix (ECM)-degrading enzymes such as matrix metalloproteases (MMPs) play an essential role in the repair of infarcted tissue, which affects ventricular remodeling after myocardial infarction. ADAMTS1 (A disintegrin and metalloprotease with thrombospondin motifs), a newly discovered metalloprotease, was originally cloned from a cancer cell line, but little is known about its contribution to disease. To test the hypothesis that ADAMTS1 appears in infarcted myocardial tissue, we examined ADAMTS1 mRNA expression in a rat myocardial infarction model by Northern blotting, real-time RT-PCR and in situ hybridization. Normal endothelium expressed little ADAMTS1 mRNA, while normal myocardium expressed no detectable ADAMTS1 mRNA. Up-regulation of ADAMTS1 was demonstrated by Northern blot analysis and real-time RT-PCR at 3 h after coronary artery ligation. In situ hybridization revealed strong ADAMTS1 mRNA signals in the endothelium and myocardium in the infarcted heart, mainly in the infarct zone, at 3 h after myocardial infarction. The rapid and transient up-regulation of the ADAMTS1 gene in the ischemic heart was distinct from the regulatory patterns of other MMPs. Our study demonstrated that the ADAMTS1 gene is a new early immediate gene expressed in the ischemic endothelium and myocardium.