Recently,
cathepsin B has been demonstrated to be involved in
myocardial infarction (MI). This study aimed to elucidate the effects of a specific
cathepsin B inhibitor,
CA-074Me, on cardiac dysfunction, remodeling and
fibrosis following MI in a rat model. Furthermore, the potential mechanisms of action of this inhibitor were investigated. In the present study, Sprague-Dawley rats were anesthetized and subjected to a
sham operation or left anterior descending coronary artery
ligation, followed by
intraperitoneal injection of
CA-074Me (10 mg/kg/day) or an equal volume of vehicle for 4 weeks. Activation of the
cathepsin B and NLRP3 pathway was detected. Cardiac function was assessed by echocardiography, while
hypertrophy and
fibrosis were determined by Masson's trichrome, immunofluorescence and morphometry. The results demonstrated that
cathepsin B-NLRP3 activation was inhibited by
CA-074Me treatment. Following such treatment for 4 weeks, the rats demonstrated smaller decreases in cardiac function, and a decrease in cardiomyocyte
hypertrophy and the level of
fibrosis.
Cathepsin B inhibition significantly attenuated cardiac dysfunction, and reduced cardiomyocyte size and cardiac
fibrosis in the experimental MI model, by inhibiting NLRP3 activation. This suggested that targeting the
cathepsin B-NLRP3 pathway may represent a novel therapeutic strategy to prevent
heart failure and remodeling following MI.