Cysteine Protease Cathepsins in Atherosclerosis and Abdominal Aortic Aneurysm

Abstract

Extracellular matrix remodeling is an important mechanism in the initiation and progression of cardiovascular diseases. Cysteine protease cathepsins are among the important proteases that affect major events in the pathogenesis of atherosclerosis and abdominal aortic aneurysm, including smooth muscle cell transmigration through elastic lamina, macrophage foam cell formation, vascular cell and macrophage apoptosis, and plaque rupture. These events have been studied in cathepsin deficiencies and cathepsin inhibitor deficiencies in mice and have provided invaluable insights regarding the roles of cathepsins in cardiovascular diseases. Pharmacological inhibitions for cathepsins are under evaluation for other human diseases and may be used as clinical treatments for cardiovascular diseases in the near future. This article reviews different mechanisms for cathepsins in atherosclerosis and abdominal aortic aneurysm that could be targeted by selective cathepsin inhibitors.

Fig. 1

Overview of potential mechanisms for cathepsins in the pathogenesis of atherosclerosis and abdominal aortic aneurysms. Cathepsins expressed in inflammatory cells, vascular smooth muscle cells (SMC), and endothelial cells (EC) degrade elastin and collagen, which may affect lesion stability, SMC migration, and leukocyte transmigration. Cathepsins are involved in antigen presentation and may increase low-density lipoprotein (LDL) retention to extracellular matrix, foam cell formation, and vascular cell apoptosis