Increased Expression of Elastolytic Cysteine Proteases, Cathepsins S and K, in the Neointima of Balloon-Injured Rat Carotid Arteries

Xian Wu Cheng, Masafumi Kuzuya, Takeshi Sasaki, Koji Arakawa, Shigeru Kanda, Daigo Sumi, Teruhiko Koike, Keiko Maeda, Norika Tamaya-Mori, Guo Ping Shi, Noboru Saito, Akihisa Iguchi

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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.

Original languageEnglish
Pages (from-to)243-251
Number of pages9
JournalAmerican Journal of Pathology
Volume164
Issue number1
DOIs
Publication statusPublished - Jan 2004

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Cheng, X. W., Kuzuya, M., Sasaki, T., Arakawa, K., Kanda, S., Sumi, D., Koike, T., Maeda, K., Tamaya-Mori, N., Shi, G. P., Saito, N., & Iguchi, A. (2004). Increased Expression of Elastolytic Cysteine Proteases, Cathepsins S and K, in the Neointima of Balloon-Injured Rat Carotid Arteries. American Journal of Pathology, 164(1), 243-251. https://doi.org/10.1016/S0002-9440(10)63114-8