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J. Biochem, 2004, Vol. 136, No. 4 439-446
© 2004 The Japanese Biochemical Society


CELL

Dynamic Induction of ADAMTS1 Gene in the Early Phase of Acute Myocardial Infarction

Keigo Nakamura1, Satoshi Hirohata1,2,*, Takashi Murakami1, Toru Miyoshi1, Kadir Demircan2, Toshitaka Oohashi2, Hiroko Ogawa1,2, Kazuya Koten1, Kenichi Toeda1, Shozo Kusachi1,3, Yoshifumi Ninomiya2 and Yasushi Shiratori1

1 Department of Medicine and Medical Science and 2 Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558; and 3 Department of Medical Technology, Okayama University Medical School of Health Science

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.

* To whom correspondence should be addressed. Tel: +81-86-235-7129, Fax: +81-86-225-5991, E-mail: hirohas{at}cc.okayama-u.ac.jp


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