title: Clinical significance of cathepsin L and cathepsin B in dilated cardiomyopathy.
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.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, Room No. 3009, New Delhi, 110029, India.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Mehra
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, Room No. 3009, New Delhi, 110029, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, Room No. 3009, New Delhi, 110029, India.
authors.forename: Mansi
authors.initials: M
authors.lastname: Manchanda
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, Room No. 3009, New Delhi, 110029, India.
authors.forename: Ratnakar
authors.initials: R
authors.lastname: Singh
authors.affiliation: Department of Biostastics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Thakur
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Rani
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Sudheer
authors.initials: S
authors.lastname: Arava
authors.affiliation: Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Narang
authors.affiliation: Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Dharamvir Singh
authors.initials: DS
authors.lastname: Arya
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, Room No. 3009, New Delhi, 110029, India. s_s_chauhan@hotmail.com.
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Chauhan
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002311:Cardiomyopathy, Dilated / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D002401:Cathepsin B / Q000097:blood*; D056668:Cathepsin L / Q000097:blood*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000009:adverse effects*; D004452:Echocardiography; D005260:Female; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051381:Rats; D013318:Stroke Volume; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D004317:Doxorubicin; C533912:CTSB protein, human; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L
keywords: Cathepsin B; Cathepsin L; Dilated cardiomyopathy; Doxorubicin; Extracellular matrix and cardiac remodeling; PBMCs