Document Detail


The expression and localization of membrane type-1 matrix metalloproteinase in human abdominal aortic aneurysms.
MedLine Citation:
PMID:  11496285     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND OBJECTIVE: Matrix metalloproteinase-2 (MMP-2) degrades both fibrillar collagens and elastin. MMP-2 is secreted as a latent 72-kd proenzyme that must be proteolytically processed to the 62-kd active form. In our laboratory we demonstrated a significant increase of active, matrix-bound MMP-2 in abdominal aortic aneurysmal (AAA) tissue compared with nonaneurysmal aorta with arteriosclerotic occlusive disease and normal aortic tissue. This increase in active MMP-2 is considered to be important in aneurysm pathogenesis, but the mechanism of its activation in aortic tissue is unknown. Membrane type-1 MMP (MT-1 MMP) is known to be an activator of MMP-2. The purpose of this study was to determine MT-1 MMP expression and its involvement in pro-MMP-2 activation in human aneurysmal tissue.
METHODS: Infrarenal aortic tissue was obtained during the surgical repair of AAAs or the bypass of aortoiliac occlusive disease, or from nondiseased aorta, and the expression of MT-1 MMP messenger RNA was determined with Northern blot analysis. MT-1 MMP protein was determined with immunoblot and immunohistochemistry. The ability of aortic tissue to activate pro-MMP-2 was analyzed by incubating aortic tissue with exogenous radiolabeled pro-MMP-2.
RESULTS: MT-1 MMP messenger RNA and protein are increased in AAA (P <.05) compared with arteriosclerotic occlusive disease and normal aortic tissue. Immunohistochemical analysis localized MT-1 MMP to aortic smooth muscle cells and macrophages in aneurysmal tissue. AAA tissue demonstrated a greater capacity to activate exogenous pro-MMP-2 compared with atherosclerotic and normal aortic tissue (P <.05).
CONCLUSION: These studies demonstrate that MT-1 MMP is increased in AAA tissue and suggest that it may be important in AAA pathogenesis through its ability to activate pro-MMP-2
Authors:
A Nollendorfs; T C Greiner; H Nagase; B T Baxter
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of vascular surgery     Volume:  34     ISSN:  0741-5214     ISO Abbreviation:  J. Vasc. Surg.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-08-09     Completed Date:  2001-10-04     Revised Date:  2012-10-03    
Medline Journal Info:
Nlm Unique ID:  8407742     Medline TA:  J Vasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  316-22     Citation Subset:  IM    
Affiliation:
Department of Surgery, University of Nebraska Medical Center, Omaha 68198-7690, USA.
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MeSH Terms
Descriptor/Qualifier:
Aorta, Abdominal / cytology
Aortic Aneurysm, Abdominal / metabolism*
Cells, Cultured
Humans
Matrix Metalloproteinase 1 / biosynthesis*,  genetics
Matrix Metalloproteinase 2 / physiology*
RNA, Messenger / analysis
Grant Support
ID/Acronym/Agency:
1RO1HL62400-01A1/HL/NHLBI NIH HHS; AR39189/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.7/Matrix Metalloproteinase 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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