Legumain and cathepsin-L expression in human unstable carotid plaque

K. L. Mattock, P. J. Gough, J. Humphries, K. Burnand, L. Patel, K. E. Suckling, F. Cuello, C. Watts, M. Gautel, M. Avkiran, A. Smith

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    Abstract

    Objective: The cysteine protease, legumain, is thought to have a role in the processing and activation of proteases such as cathepsin-L, which have been implicated in plaque rupture. This study aimed to determine: if legumain activity is up-regulated in unstable areas of plaque; the effect of legumain overexpression on the activity of cathepsin-L and the effect of mutation of the legumain RGD sequence on its cellular location.

    Methods and results: Legumain was measured in human carotid plaque extracts (n = 17) using a novel ELISA and modified activity assay. Unstable regions of plaque contained more than twice the amount of legumain protein (P < 0.001) and activity (P < 0.03) compared with stable regions of the same plaque. Overexpression of legumain in THP-1 macrophages using an adenoviral construct resulted in the processing of cathepsin-L from its 30 kDa to its 25 kDa form compared with controls.

    Conclusion: Unstable regions of plaque contain increased levels of active legumain. Over-expression of legumain in macrophages alters intracellular processing of cathepsin-L to its mature 25 kDa form. This may be a means by which legumain could contribute to plaque instability. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

    Original languageEnglish
    Pages (from-to)83-89
    Number of pages7
    JournalAtherosclerosis
    Volume208
    Issue number1
    DOIs
    Publication statusPublished - Jan 2010

    Keywords

    • Atherosclerosis
    • Carotid artery
    • Macrophages
    • Proteases
    • RGD
    • ASPARAGINYL ENDOPEPTIDASE
    • ATHEROSCLEROTIC PLAQUES
    • MAMMALIAN LEGUMAIN
    • MACROPHAGES
    • CELLS
    • MICE
    • ELECTROPHORESIS
    • PROTEINASES
    • DEGRADATION
    • ACTIVATION

    Cite this

    Mattock, K. L., Gough, P. J., Humphries, J., Burnand, K., Patel, L., Suckling, K. E., Cuello, F., Watts, C., Gautel, M., Avkiran, M., & Smith, A. (2010). Legumain and cathepsin-L expression in human unstable carotid plaque. Atherosclerosis, 208(1), 83-89. https://doi.org/10.1016/j.atherosclerosis.2009.07.022