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J Atheroscler Thromb. 2018 Feb 1;25(2):111-123. doi: 10.5551/jat.RV17016. Epub 2017 Oct 5.

Cysteine Protease Cathepsins in Atherosclerotic Cardiovascular Diseases.

Wu H1, Du Q2, Dai Q3, Ge J1, Cheng X4,5,6.

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Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University.
Department of Nephrology, Tongji Hospital, Tongji University.
Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine.
Department of Cardiology, Yanbian University Hospital.
Institute of Innovation for Future Society, Nagoya University, Graduate School of Medicine.
Division of Cardiology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea.


Atherosclerotic cardiovascular disease (ASCVD) is an inflammatory disease characterized by extensive arterial wall matrix protein degradation. Cysteine protease cathepsins play a pivotal role in extracellular matrix (ECM) remodeling and have been implicated in the development and progression of atherosclerosis-based cardiovascular diseases. An imbalance in expression between cathepsins (such as cathepsins S, K, L, C) and their inhibitor cystatin C may favor proteolysis of ECM in the pathogenesis of cardiovascular disease such as atherosclerosis, aneurysm formation, restenosis, and neovascularization. New insights into cathepsin functions have been made possible by the generation of knockout mice and by the application of specific inhibitors. Inflammatory cytokines regulate the expression and activities of cathepsins in cultured vascular cells and macrophages. In addition, evaluations of the possibility of cathepsins as a diagnostic tool revealed that the circulating levels of cathepsin S, K, and L, and their endogenous inhibitor cystatin C could be promising biomarkers in the diagnosis of coronary artery disease, aneurysm, adiposity, peripheral arterial disease, and coronary artery calcification. In this review, we summarize the available information regarding the mechanistic contributions of cathepsins to ASCVD.


Aneurysm; Atherosclerosis; Cathepsins; Neovascularization; Restenosis

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