Dynamic induction of ADAMTS1 gene in the early phase of acute myocardial infarction.
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.
Nakamura
Keigo
K
Department of Medicine and Medical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
Hirohata
Satoshi
S
Murakami
Takashi
T
Miyoshi
Toru
T
Demircan
Kadir
K
Oohashi
Toshitaka
T
Ogawa
Hiroko
H
Koten
Kazuya
K
Toeda
Kenichi
K
Kusachi
Shozo
S
Ninomiya
Yoshifumi
Y
Shiratori
Yasushi
Y
D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; D020816:Amino Acid Motifs; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D018076:DNA, Complementary / Q000378:metabolism; D004195:Disease Models, Animal; D019483:Disintegrins / Q000096:biosynthesis*; D004727:Endothelium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D017403:In Situ Hybridization; D008297:Male; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D009203:Myocardial Infarction / Q000201:enzymology* / Q000473:pathology; D017202:Myocardial Ischemia / Q000201:enzymology* / Q000473:pathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation
D018076:DNA, Complementary; D019483:Disintegrins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D012313:RNA; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human; D008666:Metalloendopeptidases