title: Cathepsin V, a novel and potent elastolytic activity expressed in activated macrophages.
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.
authors.affiliation: Department of Human Genetics, Mount Sinai School of Medicine, 5th Avenue, 100th Street, New York, NY 10029, USA.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: Li
authors.forename: Doron
authors.initials: D
authors.lastname: Greenbaum
authors.forename: Matthew
authors.initials: M
authors.lastname: Bogyo
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Weber
authors.forename: Dieter
authors.initials: D
authors.lastname: Brömme
mesh_terms: D000818:Animals; D001158:Arteries / Q000473:pathology; D001665:Binding Sites; D001667:Binding, Competitive; D015153:Blotting, Western; D020134:Catalytic Domain; D056657:Cathepsin K; D056668:Cathepsin L; D002403:Cathepsins / Q000096:biosynthesis* / Q000737:chemistry* / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000737:chemistry; D003224:Congo Red / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000096:biosynthesis* / Q000737:chemistry* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004549:Elastin / Q000737:chemistry / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D010206:Papain / Q000737:chemistry; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors
chemical_list: D006025:Glycosaminoglycans; D012333:RNA, Messenger; D011994:Recombinant Proteins; D003224:Congo Red; D012965:Sodium Chloride; D002809:Chondroitin Sulfates; D004549:Elastin; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C534278:Ctsl protein, mouse; D010206:Papain; C028217:cathepsin S; C534130:CTSK protein, human; D056657:Cathepsin K; C534132:Ctsk protein, mouse; C117627:CTSV protein, human; D020778:Matrix Metalloproteinase 2