title: Increased expression of elastolytic cysteine proteases, cathepsins S and K, in the neointima of balloon-injured rat carotid arteries.
abstract: The matrix-degrading activity of several proteases are involved in the accelerated breakdown of extracellular matrix associated with vascular remodeling during the development of atherosclerosis and vascular injury-induced neointimal formation. Previous studies have shown that the potent elastolytic cysteine proteases, cathepsins S and K, are overexpressed in atherosclerotic lesions in human and animal models. However, the role of these cathepsins in vascular remodeling remains unclear. In the present study, the expressions of cathepsin S and K and their inhibitor cystatin C were examined during arterial remodeling using a rat carotid artery balloon-injury model. The increase in both cathepsin S and K mRNA levels was observed from day 1 and day 3 through day 14 following the induction of balloon injury, respectively. Western blotting analysis revealed that both cathepsin S and K protein levels also increased in the carotid arteries during neointima formation, coinciding with an increase elastolytic activity assayed using Elastin-Congo red, whereas, no significant change in the expressions of cystatin C mRNA and protein was observed during follow-up periods after injury. Immunohistochemistry, Western blot, and in situ hybridization showed that the increase of cathepins S and K and the decrease of cystatin C occurred preferentially in the developing neointima. These findings suggest that cathepsin S and K may participate in the pathological arterial remodeling associated with restenosis.
authors.affiliation: Department of Geriatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Xian Wu
authors.initials: XW
authors.lastname: Cheng
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kuzuya
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Koji
authors.initials: K
authors.lastname: Arakawa
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kanda
authors.forename: Daigo
authors.initials: D
authors.lastname: Sumi
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Koike
authors.forename: Keiko
authors.initials: K
authors.lastname: Maeda
authors.forename: Norika
authors.initials: N
authors.lastname: Tamaya-Mori
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Shi
authors.forename: Noboru
authors.initials: N
authors.lastname: Saito
authors.forename: Akihisa
authors.initials: A
authors.lastname: Iguchi
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D015153:Blotting, Western; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology*; D002403:Cathepsins / Q000096:biosynthesis*; D055316:Cystatin C; D015891:Cystatins / Q000096:biosynthesis; D003546:Cysteine Endopeptidases / Q000096:biosynthesis*; D004195:Disease Models, Animal; D004549:Elastin / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D004790:Enzyme Induction / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar
chemical_list: C525030:CST3 protein, human; C525032:Cst3 protein, rat; D055316:Cystatin C; D015891:Cystatins; D004549:Elastin; D002403:Cathepsins; D003546:Cysteine Endopeptidases