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

doi:10.1016/j.atherosclerosis.2009.07.022

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

Research output: Contribution to journal › Article › peer-review

52 Citations (Scopus)

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 language	English
Pages (from-to)	83-89
Number of pages	7
Journal	Atherosclerosis
Volume	208
Issue number	1
DOIs	https://doi.org/10.1016/j.atherosclerosis.2009.07.022
Publication status	Published - Jan 2010

Keywords

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

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10.1016/j.atherosclerosis.2009.07.022

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title = "Legumain and cathepsin-L expression in human unstable carotid plaque",

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.",

keywords = "Atherosclerosis, Carotid artery, Macrophages, Proteases, RGD, ASPARAGINYL ENDOPEPTIDASE, ATHEROSCLEROTIC PLAQUES, MAMMALIAN LEGUMAIN, MACROPHAGES, CELLS, MICE, ELECTROPHORESIS, PROTEINASES, DEGRADATION, ACTIVATION",

author = "Mattock, \{K. L.\} and Gough, \{P. J.\} and J. Humphries and K. Burnand and L. Patel and Suckling, \{K. E.\} and F. Cuello and C. Watts and M. Gautel and M. Avkiran and A. Smith",

year = "2010",

month = jan,

doi = "10.1016/j.atherosclerosis.2009.07.022",

language = "English",

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pages = "83--89",

journal = "Atherosclerosis",

issn = "0021-9150",

publisher = "Elsevier",

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TY - JOUR

T1 - Legumain and cathepsin-L expression in human unstable carotid plaque

AU - Mattock, K. L.

AU - Gough, P. J.

AU - Humphries, J.

AU - Burnand, K.

AU - Patel, L.

AU - Suckling, K. E.

AU - Cuello, F.

AU - Watts, C.

AU - Gautel, M.

AU - Avkiran, M.

AU - Smith, A.

PY - 2010/1

Y1 - 2010/1

N2 - 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.

AB - 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.

KW - Atherosclerosis

KW - Carotid artery

KW - Macrophages

KW - Proteases

KW - RGD

KW - ASPARAGINYL ENDOPEPTIDASE

KW - ATHEROSCLEROTIC PLAQUES

KW - MAMMALIAN LEGUMAIN

KW - MACROPHAGES

KW - CELLS

KW - MICE

KW - ELECTROPHORESIS

KW - PROTEINASES

KW - DEGRADATION

KW - ACTIVATION

U2 - 10.1016/j.atherosclerosis.2009.07.022

DO - 10.1016/j.atherosclerosis.2009.07.022

M3 - Article

C2 - 19671471

SN - 0021-9150

VL - 208

SP - 83

EP - 89

JO - Atherosclerosis

JF - Atherosclerosis

IS - 1

ER -

Legumain and cathepsin-L expression in human unstable carotid plaque

Abstract

Keywords

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