Dynamic Induction of ADAMTS 1 Gene in the Early Phase of Acute Myocardial Infarction

Abstract

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. ADAMTS 1 (A aisintegrin and metalloprotease with thrombo-spondin 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 ADAMTS 1 appears in infarcted myocardial tissue, we examined ADAMTS 1 mRNA expression in a rat myocardial infarction model by Northern blotting, real-time RT PCR and in situ hybridization. Normal endothelium expressed little ADAMTS 1 mRNA, while normal myocardium expressed no detectable ADAMTS 1 mRNA. Up-regulation of ADAMTS 1 was demonstrated by Northern blot analysis and real-time RT PCR at 3h after coronary artery ligation. In situ hybridization revealed strong ADAMTS 1 mRNA signals in the endothelium and myocardium in the infarcted heart, mainly in the infarct zone, at 3h after myocardial infarction. The rapid and transient up-regulation of the ADAMTSI gene in the ischemic heart was distinct from the regulatory patterns of other MMPs. Our study demonstrated that the ADAMTS 1 gene is a new early immediate gene expressed in the ischemic endothelium and myocardium.