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PO1-2-75

Regulatory mechanisms for expression of matricryptins after myocardial infarction in rats

[Speaker] Akira Sugiyama:1
[Co-author] Ayaka Mitsui:1, Muneyoshi Okada:1, Hideyuki Yamawaki:1
1:Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Japan

Background: Background: An imbalance between production and degradation of extracellular matrix (ECM) leads to pathological cardiac remodeling during the development of cardiac diseases. Matricryptins are bioactive cleaved fragments released from ECM by ECM degrading enzymes, such as matrix metalloproteinases (MMPs) and cathepsins. The expression of matricryptins increases in some experimental cardiac disease models including myocardial infarction. The aim of this study was to clarify the regulatory mechanisms for expression of arresten and canstatin which are basement membrane-derived matricryptins cleaved from α1 and α2 chain of type IV collagen, respectively, after myocardial infarction in rats.
Methods: Myocardial infarction (MI) was induced by ligating the left anterior descending artery in male Wistar rats. One or three days after operation, ventricles were isolated and separated into the infarcted and non-infarcted area. Western blotting and immunohistochemical analyses were performed to determine the protein expression of arresten, canstatin, MMP-9 and cathepsin S. Protein expression of arresten and canstatin 3 days after MI in cathepsin S small interference (si) RNA or control siRNA-injected rats were analyzed by Western blotting.
Results: The protein expression of arresten and canstatin decreased in the infarcted area 1 and 3 days after MI compared with the non-infarcted area. The protein expression of cathepsin S which is known to degrade arresten and canstatin significantly increased in the infarcted area 1 and 3 days after MI compared with the non-infarcted area. The protein expression of MMP-9, a degrading enzyme for type IV collagen, also increased in the infarcted area. The protein expression of arresten and canstatin did not decrease in the infarcted area of cathepsin S siRNA-injected rats.
Conclusion: We for the first time demonstrated that the protein expression of arresten and canstatin decreases in the infarcted area after MI, while the protein expression of cathepsin S and MMP-9 increased. It is indicated that the protein expression of arresten and canstatin might be regulated by cathepsin S. Further research on the detailed regulatory mechanisms for expression of matricryptins could shed light on understanding the pathogenesis of MI and lead to a development of new drugs for MI.

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