Cathepsin V, a novel and potent elastolytic activity expressed in activated macrophages
- Details
- Publication Year 2004-08-27,Volume 279,Issue #35,Page 36761-36770
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Publication Type
- Journal Article
- Abstract
- Atherosclerosis is characterized by a thickening and loss of elasticity of the arterial wall. Loss of elasticity has been attributed to the degradation of the arterial elastin matrix. Cathepsins K and S are papain-like cysteine proteases with known elastolytic activities, and both enzymes have been identified in macrophages present in plaque areas of diseased blood vessels. Here we demonstrate that macrophages express a third elastolytic cysteine protease, cathepsin V, which exhibits the most potent elastase activity yet described among human proteases and that cathepsin V is present in atherosclerotic plaque specimens. Approximately 60% of the total elastolytic activity of macrophages can be attributed to cysteine proteases with cathepsins V, K, and S contributing equally. From this 60%, two-thirds occur extracellularly and one-third intracellularly with the latter credited to cathepsin V. Ubiquitously expressed glycosaminoglycans (GAGs) such as chondroitin sulfate specifically inhibit the elastolytic activities of cathepsins V and K via the formation of specific cathepsin-GAG complexes. In contrast, cathepsin S, which does not form complexes with chondroitin sulfate is not inhibited; thus suggesting a specific regulation of elastolytic activities of cathepsins by GAGs. Because the GAG content is reduced in atherosclerotic plaques, an increase of cathepsins V and K activities may accelerate the destruction of the elastin matrix in diseased arteries.
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Keywords
- CYSTEINE PROTEASE; FUNCTIONAL EXPRESSION; ENZYMATIC CHARACTERIZATION; MATRIX METALLOPROTEINASES; ATHEROSCLEROTIC PLAQUES; CHONDROITIN SULFATES; MOLECULAR-CLONING; INVARIANT CHAIN; VINYL SULFONES; DEFICIENT MICE
- Publisher's Version
- https://doi.org/10.1074/jbc.M403986200
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2004-08-27 12:00:00