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Enhanced myocardial cathepsin B expression in patients with dilated cardiomyopathy
Junbo Ge1, Gang Zhao, Ruizhen Chen
1Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Fenglin Road 180, Shanghai 200032, PR China. gejunbo@zshospital.net
Insights
Heart failure is linked to increased levels of cathepsin B, a lysosomal protease. This finding suggests cathepsin B may contribute to the development of heart failure.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Cathepsin B is a lysosomal protease implicated in apoptosis and myofibrillar protein degradation during myocardial infarction.
- Understanding its role in human heart failure is crucial for therapeutic development.
Purpose of the Study:
- To investigate myocardial cathepsin B expression in failing and non-failing human hearts.
- To explore the correlation between cathepsin B levels and heart function.
Main Methods:
- Analysis of left ventricle tissue samples from heart failure patients and non-failing donors.
- Quantification of cathepsin B expression using immunohistochemistry, RT-PCR, and Western blotting.
- Assessment of apoptosis via TUNEL staining.
Main Results:
- Cathepsin B expression (mRNA and protein) was significantly elevated in failing hearts compared to non-failing hearts.
- Higher cathepsin B levels negatively correlated with ejection fraction (EF) in heart failure patients.
- The apoptotic index was significantly higher in failing hearts.
Conclusions:
- Increased myocardial cathepsin B expression is observed in human heart failure.
- Cathepsin B may play a role in the pathogenesis and progression of heart failure.
Objective:
Cathepsin B is a prominent lysosomal protease and is involved in apoptosis as well as degradation of myofibrillar proteins in myocardial infarction. The aim of this study was to investigate myocardial cathepsin B expression in failing and non-failing human hearts.
Methods:
Tissue samples were taken from transplanted left ventricles from 20 patients with dilated cardiomyopathy and 5 non-failing donor hearts that could not be transplanted for technical reasons. Myocardial cathepsin B expression was determined by immunohistochemistry, the reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Apoptosis was assessed by TUNEL staining.
Results:
Positive cathepsin B staining was found in failing and non-failing hearts. The expression of cathepsin B at mRNA and protein levels was significantly higher in failing hearts compared with non-failing hearts. Correlation analysis revealed that cathepsin B at mRNA and protein levels negatively correlated with EF (r=0.66, p=0.002 and r=0.492, p=0.028, respectively) in patients with heart failure. The apoptotic index was 0.015+/-0.006 in failing hearts and 0.002+/-0.001 in non-failing hearts (p<0.01).
Conclusion:
Increased myocardial expression of cathepsin B was found in patients with heart failure suggesting that cathepsin B might play a role in the genesis and development of heart failure.
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