Document Detail

Comparative proteomics reveals a systemic vulnerability in the vasculature of patients with abdominal aortic aneurysms.
MedLine Citation:
PMID:  21741794     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Abdominal aortic aneurysms (AAA) are associated with inflammation, apoptosis, and matrix degradation. AAA tissue represents the end stage of disease, limiting its utility in identification of factors culpable for initiation of aneurysm development. Recent evidence suggests that AAAs are a local representation of a systemic disease of the vasculature. Morphologic and molecular changes, comparable to those found in the aneurysm wall, have been demonstrated in veins from patients with AAAs. Changes in the vascular tissue proteome of patients with AAAs were investigated, using inferior mesenteric vein (IMV), to gain insight into early molecular changes contributing to AAA development.
METHODS: IMV was harvested from 16 patients with AAA and 16 matched controls. Whole IMV lysates were subjected to 2-D difference in gel electrophoresis (2D-DIGE) with quantitative densitometry. Protein spots differentially expressed in AAA were identified using mass spectrometry. Differential protein expression was validated by Western blotting and localized to cell type by immunohistochemistry (IHC).
RESULTS: Decreased levels of prohibitin (AAA, 2.00 ± 1.37; controls, 3.81 ± 1.39; 1.9-fold change; P = .02) AAA (7.33 ± 3.9; controls, 14.5 ± 5.6; 2-fold change; P = .001), along with relative increases in a cleaved fragment of vimentin (AAA, 12.9 ± 9; controls, 6.9 ± 4.7; 2-fold change; P = .11) were identified in AAA patients. All proteins were localized to the vascular smooth muscle cells.
CONCLUSIONS: Proteins important in combating the injurious effects of oxidative stress and modulating the response to inflammation appear reduced in the vasculature of patients with AAA. These changes may represent early events in AAA formation. Enhancing expression of these proteins might offer a novel therapeutic avenue to inhibit AAA development.
Ian M Nordon; Robert J Hinchliffe; Amir H Malkawi; Grisha Pirianov; Evelyn Torsney; Ian M Loftus; Gillian W Cockerill; Matt M Thompson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-07-13
Journal Detail:
Title:  Journal of vascular surgery     Volume:  54     ISSN:  1097-6809     ISO Abbreviation:  J. Vasc. Surg.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-05     Completed Date:  2011-11-18     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:  1100-1108.e6     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.
St. George's Vascular Institute, St. James' Wing, St. George's Hospital, London, United Kingdom.
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MeSH Terms
Annexin A1 / analysis
Aorta, Abdominal / chemistry
Aortic Aneurysm, Abdominal / metabolism*
Blotting, Western
Case-Control Studies
Electrophoresis, Gel, Two-Dimensional
Mass Spectrometry
Mesenteric Veins / chemistry
Middle Aged
Muscle, Smooth, Vascular / chemistry*
Myocytes, Smooth Muscle / chemistry*
Proteins / analysis*
Proteomics* / methods
Repressor Proteins / analysis
Reproducibility of Results
Vimentin / analysis
Reg. No./Substance:
0/Annexin A1; 0/Proteins; 0/Repressor Proteins; 0/Vimentin; 0/prohibitin

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