| Comparative proteomics reveals a systemic vulnerability in the vasculature of patients with abdominal aortic aneurysms. | |
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MedLine Citation:
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PMID: 21741794 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. CLINICAL RELEVANCE: AAA is a preventable cause of death. Molecular and histological studies have provided great insight into the features of large aneurysms. However, little is known about factors initiating aneurysm development. Genetic studies have failed to identify causal genes or specific nucleotide polymorphisms culpable for aneurysm initiation. Proteomics provides an insight into cellular changes down-stream of genetic code. This study uses proteomic techniques to establish protein changes in the vasculature that may be involved in AAA development. The future of AAA treatment may be pharmacological whereby altered protein expression could be modified to prevent aneurysm progression or rupture. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2011-7-7 |
Journal Detail:
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Title: Journal of vascular surgery : official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter Volume: - ISSN: 1097-6809 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8407742 Medline TA: J Vasc Surg Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved. |
Affiliation:
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St. George's Vascular Institute, St. James' Wing, St. George's Hospital, London, United Kingdom. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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