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

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

doi:10.1016/s0002-9440(10)63114-8

Cited by 86 publications

(95 citation statements)

References 37 publications

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“…45 Another possible explanation is that attenuation of the inflammatory response by AP caused reduced vein wall injury, or AP inhibited other matrix enzymes such as cathepsins or serum elastase. 46 The latter contribution may be most important, and is a subject of future study.…”

Section: Discussionmentioning

confidence: 98%

Plasmin Inhibition Increases MMP-9 Activity and Decreases Vein Wall Stiffness During Venous Thrombosis Resolution

Dewyer

Sood

Lynch

et al. 2007

Journal of Surgical Research

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Section: Discussionmentioning

confidence: 98%

Plasmin Inhibition Increases MMP-9 Activity and Decreases Vein Wall Stiffness During Venous Thrombosis Resolution

Dewyer

Sood

Lynch

et al. 2007

Journal of Surgical Research

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“…Cat S exhibits pronounced elastolytic and collagenolytic activities in vitro and in vivo [21] . Cheng et al [11] showed that Cat S is expressed at only a low level in the LV myocardium of control rats or normal humans.…”

Section: Discussionmentioning

confidence: 99%

Simvastatin inhibited cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice fed a “Western-style diet” by increasing PPAR α and γ expression and reducing TC, MMP-9, and Cat S levels

Qin

et al. 2010

Acta Pharmacol Sin

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Aim:The examine the cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice (ApoE-/-mice) fed a "Western-style diet" and the effect of simvastatin intervention. Methods: Male ApoE-/-mice (n=36) were fed a "Western-style diet" from the age of 8 weeks. After 16 weeks, they were randomly given either simvastatin (25 mg·kg -1 ·d -1 ) or normal saline (control group) by gavage for 8, 16, or 24 weeks. The left ventricular (LV) wall thickness and diameter of the myocardial cells were determined with Hematoxylin-Eosin stain, and the level of fibrosis of the myocardial matrix was assessed with Masson stain. Real-time quantitative polymerase chain reaction and Western blotting analysis were used to determine the mRNA and protein expression of matrix metalloproteinase-9 (MMP-9), Cathepsin S (Cat S), and the peroxisome proliferator-activated receptors (PPARs) in the myocardium of ApoE-/-mice. Results: ApoE-/-mice fed a "Western-style diet" showed an significant age-dependent increase in total cholesterol (TC), LV wall thickness, myocardial cell diameter and LV collagen content (P<0.05). The simvastatin treatment group showed significantly reduced LV wall thickness, myocardial cell diameters and LV collagen content at 40 weeks when compared with the control group (P<0.05). Furthermore, treatment with simvastatin also significantly inhibited the mRNA and protein expressions of MMP-9 and Cat S as well as increased the mRNA and protein expressions of PPAR alpha and PPAR gamma at 32 and 40 weeks compared with the control group (P<0.05) . Conclusion: ApoE-/-mice fed a "Western-style diet" had cardiac hypertrophy and fibrosis, which worsened with age. Simvastatin treatment inhibits the development of cardiac hypertrophy and fibrosis, and this effect may be mediated through increased levels of PPAR alpha and PPAR gamma and reduced levels of TC, MMP-9, and Cat S.

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“…Focus has been given to the elastolytic activities of cathepsins S and K. Both cathepsins are potent elastin-degrading proteases surpassing the in vitro activities of prototype elastases such as pancreatic, leukocyte, and metalloelastases (MMP-12). The expression of cathepsins S and K has been described in smooth muscle cells and macrophages, with both cell types being critical in the pathophysiology of the arterial vascular system (3,45). Elastin is an integral component of the intima and responsible for the elasticity of the blood vessels.…”

Section: Discussionmentioning

confidence: 99%

Cathepsin V, a Novel and Potent Elastolytic Activity Expressed in Activated Macrophages

Yasuda

Greenbaum

et al. 2004

Journal of Biological Chemistry

176

138

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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.Atherosclerosis is characterized by arterial intimal enlargement and subsequent lipid deposition leading to the formation of blood stream obstructing plaques. The infiltration of monocyte-derived macrophages (MDMs) 1 and smooth muscle cells (SMCs) into the intima of the inflamed artery contributes to the formation of atherosclerotic lesions. Atherosclerotic lesions resident MDMs and SMCs produce a large number of extracellular matrix-degrading enzymes (1), such as cysteine proteases (2-5) and matrix metalloproteinases (MMPs) (6 -8).Elastin and collagen are the two major extracellular matrix components that provide elasticity and tensile strength to the arterial wall. The destruction of elastin and collagen causes a weakening and rupture of blood vessels (9, 10). MMPs, serine, and cysteine proteases have been identified as major elastolytic proteases in arteries (11, 12). Among cysteine proteases, cathepsins S and K have been considered as the most potent elastolytic activities with cathepsin K exhibiting a slightly higher activity than cathepsin S (13, 14). However, cathepsin K-deficient human macrophages derived from patients with pycnodysostosis were shown to retain their high cysteine proteasedependent elastolytic activities (15). This finding implied that additional cathepsins may contribute to the overall elastolytic activity in human macrophages.We and others (16 -18) have identified and partially characterized a novel human cysteine protease closely related to cathepsin L that was named cathepsin V (also known as cathepsin L2). Cathepsin V shares 80% protein s...

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

Cited by 86 publications

References 37 publications

Plasmin Inhibition Increases MMP-9 Activity and Decreases Vein Wall Stiffness During Venous Thrombosis Resolution

Plasmin Inhibition Increases MMP-9 Activity and Decreases Vein Wall Stiffness During Venous Thrombosis Resolution

Simvastatin inhibited cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice fed a “Western-style diet” by increasing PPAR α and γ expression and reducing TC, MMP-9, and Cat S levels

Cathepsin V, a Novel and Potent Elastolytic Activity Expressed in Activated Macrophages

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