Clinical significance of cathepsin L and cathepsin B in dilated cardiomyopathy

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10 Scopus citations

Abstract

Dysregulated expression of lysosomal cysteine cathepsins is associated with adverse cardiac remodeling, a characteristic of several cardiovascular diseases. However, the information regarding the role of cysteine cathepsin L (CTSL) and cathepsin B (CTSB) in dilated cardiomyopathy (DCM) is limited. The present study was aimed to investigate the expression of CTSL and CTSB in animal model of doxorubicin (doxo)-induced cardiomyopathy as well as in peripheral blood samples of DCM patients. Cardiac tissue sections from doxo-treated and control rats were used to study the expression of CTSL and CTSB by enzyme assay and immunohistochemistry (IHC). Peripheral blood mononuclear cells (PBMCs) isolated from DCM patients (n = 29) along with age-matched healthy controls (n = 28) were used to assay enzymatic activity of these cathepsins. Activities of these proteases were further correlated with echocardiographic parameters of DCM patients. A significant increase in CTSL activity and protein expression was observed with no changes in CTSB levels in doxo-treated rats as compared to controls. We also observed a drastic increase in the functional activity of cathepsin L+cathepsin B (CTSL+B), CTSL, and CTSB in DCM patients compared to controls (p ≤ 0.001). Increased levels of these proteases exhibited a statistically significant correlation with reduced left ventricular ejection fraction (LVEF) in DCM patients (ρ = −0.58, p = 0.01). For the first time, this study demonstrates a correlation between increased expression of CTSL and CTSB in PBMCs with severity of left ventricular dysfunction in DCM patients. Thus, these proteases may serve as blood-based biomarker of DCM and prove useful in its management.

Original languageEnglish (US)
Pages (from-to)139-147
Number of pages9
JournalMolecular and Cellular Biochemistry
Volume428
Issue number1-2
DOIs
StatePublished - Apr 1 2017
Externally publishedYes

Keywords

  • Cathepsin B
  • Cathepsin L
  • Dilated cardiomyopathy
  • Doxorubicin
  • Extracellular matrix and cardiac remodeling
  • PBMCs

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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