Cathepsin B in human peripheral blood lymphocytes as a peripheral biomarker for cardiac hypertrophy
Dandan Feng1, Chao Li2, Wenjuan Gao1
1Department of Geriatrics, Shandong Provincial Hospital, Shandong First Medical University, Jinan, 250021, Shandong, China.
Insights
Cathepsin B is present in peripheral blood lymphocytes (PBLs) and its levels correlate with cardiac hypertrophy. Elevated PBL cathepsin B may serve as a biomarker for diagnosing pathological cardiac hypertrophy.
Area of Science:
- Cardiovascular Biology
- Biochemistry
- Molecular Diagnostics
Background:
- Cathepsin B is upregulated in pathological cardiac hypertrophy.
- Its presence and association with hypertrophy in human peripheral blood lymphocytes (PBLs) were previously unknown.
Purpose of the Study:
- To determine if cathepsin B is detectable in human PBLs.
- To investigate the association between PBL cathepsin B levels and pathological cardiac hypertrophy.
- To evaluate cathepsin B as a potential peripheral biomarker for cardiac hypertrophy.
Main Methods:
- Immunofluorescence staining to detect cathepsin B in human PBLs.
- Western blotting and quantitative PCR to measure cathepsin B expression.
- Correlation studies, logistic regression, and ROC analysis to assess diagnostic value.
Main Results:
- Cathepsin B was confirmed in human PBLs.
- PBL cathepsin B levels positively correlated with cardiac tissue levels (r=0.441, p=0.017).
- Significantly elevated PBL cathepsin B was observed in patients with left ventricular hypertrophy, especially eccentric hypertrophy (p<0.001).
- Cathepsin B was identified as an independent risk factor for left ventricular hypertrophy (OR=4.863).
- ROC analysis indicated diagnostic value for cathepsin B in PBLs (AUC=0.748, p=0.001).
Conclusions:
- PBL cathepsin B levels correlate with myocardial cathepsin B levels.
- PBL cathepsin B is a potential peripheral biomarker for diagnosing maladaptive cardiac hypertrophy.
- Cathepsin B expression in PBLs is associated with left ventricular hypertrophy.
Abstract:
Previous studies have demonstrated that cathepsin B is up-regulated in the myocardium of both mice and humans with pathological cardiac hypertrophy. However, it remains unknown whether cathepsin B is detectable in human peripheral blood lymphocytes (PBLs) and whether its expression is associated with pathological hypertrophy. In this study, immunofluorescence staining confirmed the presence of cathepsin B in human PBLs. Western blotting analysis and correlation studies further revealed a positive correlation between cathepsin B protein levels in PBLs and that in cardiac tissues (r = 0.441, p = 0.017). We also investigated the association between cathepsin B expression level in PBLs and cardiac structure and function. Quantitative PCR and western blotting analyses indicated that patients with left ventricular hypertrophy, particularly those with eccentric hypertrophy, exhibited significantly elevated cathepsin B expression in PBLs (p < 0.001). Logistic regression analysis identified cathepsin B as an independent risk factor for left ventricular hypertrophy (odds ratio = 4.863, 95% confidence interval: 1.341-17.632). Receiver operating characteristic analysis further supported its diagnostic value (area under the curve = 0.748, p = 0.001). In summary, cathepsin B levels in PBLs positively correlates with myocardial levels and may serve as a peripheral biomarker for diagnosing maladaptive cardiac hypertrophy.
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