Cathepsin S degrades arresten and canstatin in infarcted area after myocardial infarction in rats

The basement membrane surrounding cardiomyocytes is mainly composed of α1 and α2 chain of type IV collagen. Arresten and canstatin are fragments of non-collagenous C-terminal domain of α1 and α2 chain, respectively. We previously reported that the expression of canstatin was decreased in infarcted area 2 weeks after myocardial infarction in rats. In the present study, we investigated the regulatory mechanism for expression of arresten and canstatin. Myocardial infarction model rats were produced by ligating left anterior descending artery. Western blotting and immunohistochemical staining were performed to determine the protein expression and distribution. Arresten and canstatin were highly expressed in the heart. One day and three days after myocardial infarction, the expression of arresten and canstatin in infarcted area was lower than that in non-infarcted area. The expression of cathepsin S, which is known to degrade arresten and canstatin, was increased in the infarcted area. A knockdown of cathepsin S gene using small interference RNA suppressed the decline of arresten and canstatin in the infarcted area 3 days after myocardial infarction. This study for the first time revealed that arresten and canstatin are immediately degraded by cathepsin S in the infarcted area after myocardial infarction. These findings present a novel fundamental insight into the pathogenesis of myocardial infarction through the turnover of basement membrane-derived endogenous factors.