ADAM33 expression in atherosclerotic lesions and relationship of ADAM33 gene variation with atherosclerosis
ADAM33 expression in atherosclerotic lesions and relationship of ADAM33 gene variation with atherosclerosis
A-disintegrin-and-metalloproteinase-domains (ADAMs) are membrane-anchored glycoproteins involved in cell adhesion, cell migration and proteolysis. ADAM15 has been implicated in atherosclerosis, with an effect on vascular smooth muscle cell migration. We investigated whether ADAM33, which is evolutionally closely related to ADAM15, was expressed in atheromas and whether it had an effect on vascular smooth muscle migration. We also tested whether ADAM33 gene variation had an influence on the extent of atherosclerosis in patients with coronary artery disease. Immunohistochemical analyses showed that ADAM33 was expressed in smooth muscle cells in the arterial wall and that the expression was increased in smooth muscle cells in atheromas. ADAM33 immunostaining on inflammatory cells in atheromas was also observed. Primary vascular smooth muscle cells in culture were also found to express ADAM33. Boyden chamber assays showed that a neutralising antibody against ADAM33 increased the ability of arterial smooth muscle cells to migrate through a reconstituted basement membrane, suggesting that ADAM33 has an inhibitory effect on vascular smooth muscle migration. Moreover, we detected an association between ADAM33 genotype and the extent of atherosclerosis in a large cohort of coronary artery disease patients. These findings suggest that ADAM33 is implicated in the pathogenesis of atherosclerosis.
ADAM33, smooth muscle cells, atherosclerosis, genetic, polymorphism
224-230
Holloway, John W.
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Laxton, Ross C
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Rose-Zerilli, Matthew J.
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Holloway, Judith A.
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Andrews, A. Lynn
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Riaz, Zeshan
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Wilson, Susan J.
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Simpson, Iain A
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Ye, Shu
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July 2010
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Laxton, Ross C
1448bf82-da33-4587-ab25-a036d9133825
Rose-Zerilli, Matthew J.
08b3afa4-dbc2-4c0d-a852-2a9f33431199
Holloway, Judith A.
f22f45f3-6fc8-4a4c-bc6c-24add507037c
Andrews, A. Lynn
4ddaec43-0f43-40cd-a191-aa53b0b30f16
Riaz, Zeshan
965e2063-659e-4d18-b562-d12514640b12
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Simpson, Iain A
b8754895-90e0-4966-8d42-fbc79be2782e
Ye, Shu
132b6474-1927-4f93-80db-2c620a31c1ab
Holloway, John W., Laxton, Ross C, Rose-Zerilli, Matthew J., Holloway, Judith A., Andrews, A. Lynn, Riaz, Zeshan, Wilson, Susan J., Simpson, Iain A and Ye, Shu
(2010)
ADAM33 expression in atherosclerotic lesions and relationship of ADAM33 gene variation with atherosclerosis.
Atherosclerosis, 211 (1), .
(doi:10.1016/j.atherosclerosis.2010.02.023).
Abstract
A-disintegrin-and-metalloproteinase-domains (ADAMs) are membrane-anchored glycoproteins involved in cell adhesion, cell migration and proteolysis. ADAM15 has been implicated in atherosclerosis, with an effect on vascular smooth muscle cell migration. We investigated whether ADAM33, which is evolutionally closely related to ADAM15, was expressed in atheromas and whether it had an effect on vascular smooth muscle migration. We also tested whether ADAM33 gene variation had an influence on the extent of atherosclerosis in patients with coronary artery disease. Immunohistochemical analyses showed that ADAM33 was expressed in smooth muscle cells in the arterial wall and that the expression was increased in smooth muscle cells in atheromas. ADAM33 immunostaining on inflammatory cells in atheromas was also observed. Primary vascular smooth muscle cells in culture were also found to express ADAM33. Boyden chamber assays showed that a neutralising antibody against ADAM33 increased the ability of arterial smooth muscle cells to migrate through a reconstituted basement membrane, suggesting that ADAM33 has an inhibitory effect on vascular smooth muscle migration. Moreover, we detected an association between ADAM33 genotype and the extent of atherosclerosis in a large cohort of coronary artery disease patients. These findings suggest that ADAM33 is implicated in the pathogenesis of atherosclerosis.
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Submitted date: 5 August 2009
Accepted/In Press date: 24 February 2010
Published date: July 2010
Keywords:
ADAM33, smooth muscle cells, atherosclerosis, genetic, polymorphism
Identifiers
Local EPrints ID: 79671
URI: http://eprints.soton.ac.uk/id/eprint/79671
ISSN: 0021-9150
PURE UUID: 9ede4e9d-0ec1-4e27-95e0-058c7580eb5c
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Date deposited: 18 Mar 2010
Last modified: 14 Mar 2024 02:56
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Contributors
Author:
Ross C Laxton
Author:
A. Lynn Andrews
Author:
Zeshan Riaz
Author:
Iain A Simpson
Author:
Shu Ye
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