Chonnam Med J.  2012 Aug;48(2):77-85. 10.4068/cmj.2012.48.2.77.

Cysteinyl Cathepsins: Multifunctional Enzymes in Cardiovascular Disease

• Li X
• Liu Z
• Cheng Z
• Cheng X

• KMID: 2172207
• DOI: http://doi.org/10.4068/cmj.2012.48.2.77

Abstract

Until recently, the role of lysosomal cysteine protease cathepsins in intracellular protein degradation was believed to be mainly restricted to scavenging. However, recent studies have revealed nontraditional roles for cysteine protease cathepsins in the extracellular space during the development and progression of cardiovascular disease. Although the precise mechanisms are unknown, data from animal studies suggest that members of the cathepsin family, like other extracellular proteases, contribute to extracellular matrix protein remodeling and interstitial matrix degradation, as well as to cell signaling and cell apoptosis in heart disease. Inflammatory cytokines and hormones regulate the expression and secretion of cathepsins in cultured cardiovascular cells and macrophages. Serum levels of cathepsins L, S, and K and their endogenous inhibitor cystatin C may be useful predictive biomarkers in patients with coronary artery disease and cardiac disease. Furthermore, in vivo pharmacological intervention with a synthetic cathepsin inhibitor and cardiovascular drugs (including statins and angiotensin II type 1 receptor antagonists) has the potential for pharmacologic targeting of cathepsins in cardiovascular disease. This review focuses on cathepsin biology (structure, synthesis, processing, activation, secretion, activity regulation, and function) and the involvement of cysteinyl cathepsins in the pathogenesis of several heart and vessel diseases, especially with respect to their potential application as diagnostic and prognostic markers and drug targets to prevent inappropriate proteolysis in cardiovascular disease.

Keyword

Cysteine proteases; Cathepsins; Cystatin C; Extracellular matrix proteins; Cardiovascular disease

MeSH Terms

Animals
Apoptosis
Biomarkers
Biology
Cardiovascular Agents
Cardiovascular Diseases
Cathepsins
Coronary Artery Disease
Cystatin C
Cysteine Proteases
Cytokines
Extracellular Matrix
Extracellular Matrix Proteins
Extracellular Space
Glycosaminoglycans
Heart
Heart Diseases
Humans
Macrophages
Peptide Hydrolases
Proteolysis
Receptor, Angiotensin, Type 1
Cardiovascular Agents
Cathepsins
Cystatin C
Cysteine Proteases
Cytokines
Extracellular Matrix Proteins
Glycosaminoglycans
Peptide Hydrolases
Receptor, Angiotensin, Type 1

Figure

• 

  FIG. 1 Illustration of the functions of cysteinyl cathepsins/cystatin C (Cats/CystC) in the pathogenesis of cardiovascular disease (CVD). Cats can originate from CVD-related cells and inflammatory cells under various stress and inflammatory conditions and degrade the extracellular matrix (ECM).

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