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.
Cathepsin L Cathepsin B Dilated cardiomyopathy PBMCs Doxorubicin Extracellular matrix and cardiac remodeling
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Department of Biotechnology (DBT), Govt. of India (BT/PR7146/MED/30/900/12), New Delhi, India, financially supported this study. Siddharth Mehra is a recipient of Senior Research Fellowship from University Grants Commission (U.G.C), New Delhi, India. The authors like to acknowledge Dr. Anurag Kumar and Dr. Prajwal for their help in formatting the final version of manuscript.
Compliance with ethical standards
Conflict of interest
The authors declared that they have no potential conflicts of interest.
Research involving human participants
All procedures performed in studies involving human participants were in accordance with the ethical standards of the 1964 Helsinki declaration and was approved by medical ethics review board of All India Institute of Medical Sciences, New Delhi, India.
Written informed consent was obtained from all the participants before enrollment. Similarly for the use of animal model in the present study all applicable international, national, and institutional guidelines for the proper care and use of animals were followed.
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