Atherosclerosis predisposes patients to cardiovascular diseases, such as myocardial infarction and stroke. Instigation of vascular injury is triggered by retention of lipids and inflammatory cells in the vascular endothelium. Whereas these vascular lesions develop in young adults and are mostly considered harmless, over time persistent inflammatory and remodeling processes will ultimately damage the arterial wall and cause a thrombotic event due to exposure of tissue factors into the lumen. Evidence from human tissues and preclinical animal models has clearly established the role of cathepsin cysteine proteases in the development and progression of vascular lesions. Hence, understanding the function of cathepsins in atherosclerosis is important for developing novel therapeutic strategies and advanced point of care diagnostics. In this review we will describe the roles of cysteine cathepsins in different cellular process that become dysfunctional in atherosclerosis, such as lipid metabolism, inflammation and apoptosis, and how they contribute to arterial remodeling and atherogenesis. Finally, we will explore new horizons in protease molecular imaging, which may potentially become a surrogate marker to identify future cardiovascular events.
Bibliographical noteFunding Information:
This review was supported by the United States–Israel Binational Science Foundation (BSF) (2009010 and 2011480 to GB), the European Research Council (ERC) Starting grant (337238 to GB) and the Deutsche Forschungsgemeinschaft (DFG) (MI 710/8-1 to GB).
© The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
- activity-based probes
- vascular inflammation