Cathepsin B inhibition attenuates cardiac dysfunction and remodeling following myocardial infarction by inhibiting the NLRP3 pathway Retraction in /10.3892/mmr.2017.7551

Liu,Aiguo; Gao,Xuan; Zhang,Qingbin; Cui,Lianqun

doi:10.3892/mmr.2013.1507

Cathepsin B inhibition attenuates cardiac dysfunction and remodeling following myocardial infarction by inhibiting the NLRP3 pathway

Retraction in: /10.3892/mmr.2017.7551

Authors:
- Aiguo Liu
- Xuan Gao
- Qingbin Zhang
- Lianqun Cui
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Affiliations: Department of Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China, Department of Cardiology, Shandong Yi Dou Central Hospital Affiliated to Weifang Medical College, Qingzhou, Weifang, Shandong 262500, P.R. China
Published online on: June 4, 2013 https://doi.org/10.3892/mmr.2013.1507
Pages: 361-366

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Abstract

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.

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