| The pathophysiology of abdominal aortic aneurysm growth: corresponding and discordant inflammatory and proteolytic processes in abdominal aortic and popliteal artery aneurysms. | |
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MedLine Citation:
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PMID: 20488324 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: There is remarkable controversy over the processes driving abdominal aneurysm growth. The inherent limitations of animal and human studies hamper elucidation of the key inflammatory and proteolytic processes. Human data are largely derived from surgical specimens that typically reflect the final stages of the disease process and thus do not allow distinction between primary and secondary processes. Clear epidemiologic and genetic associations between abdominal aortic aneurysm (AAA) and popliteal artery aneurysms (PAA) suggest that that these two pathologies share common grounds. On this basis, we reasoned that information of corresponding and discordant processes in these aneurysms might provide critical clues on the processes that are crucial for aneurysm progression. METHODS: Messenger RNA (semi-quantitative real-time polymerase chain reaction) and protein analysis (enzyme-linked immunosorbent assay, multiplex, Western blotting), and histology were performed on aneurysm wall samples obtained during elective PAA and AAA repair. Nonaneurysmal aorta tissue from organ donors was included as reference. RESULTS: Messenger RNA and protein analysis showed that PAA and AAA are both characterized by a marked activation of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) proinflammatory transcription factors, and hyperexpression of interleukin (IL)-6 and IL-8. Discordant findings were found for other inflammatory markers such as interferon-gamma, interferon-inducible protein 10, tumor necrosis factor-alpha, monocyte chemotactic protein-1, and macrophage inflammatory protein 1alpha and beta, which were all lower in PAA. On the cellular level, both pathologies exhibited profuse infiltration of macrophages, neutrophils, and T-helper cells. Results for B cells, plasma cells, and cytotoxic T cells were discordant, with minimal infiltration of these cell types in PAA. Evaluation of protease expression and activation showed that both conditions are dominated by increased matrix metalloproteinase 8 and 9, and cathepsin K, L and S expression and activation. CONCLUSION: This explorative study characterizes degenerative aneurysmal disease general inflammatory conditions that are dominated by profound activation of the NF-kappaB and AP-1 pathways, hyperexpression of IL-6 and IL-8, and neutrophil involvement. Discordant findings for interferon gamma, cytotoxic T cells, B cells, and plasma cells challenge a critical role for these factors in the process of aneurysm growth. Pharmaceutic strategies targeting the common components in AAA and PAA may prove effective for the stabilization of AAA. |
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Authors:
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Hazem Abdul-Hussien; Roeland Hanemaaijer; Robert Kleemann; Ben F J Verhaaren; J Hajo van Bockel; Jan H N Lindeman |
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Publication Detail:
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Type: Comparative Study; Journal Article |
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: 51 ISSN: 1097-6809 ISO Abbreviation: J. Vasc. Surg. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-21 Completed Date: 2010-06-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8407742 Medline TA: J Vasc Surg Country: United States |
Other Details:
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Languages: eng Pagination: 1479-87 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved. |
Affiliation:
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Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Aged, 80 and over Aneurysm / genetics, metabolism, pathology, physiopathology* Aorta, Abdominal / chemistry, pathology, physiopathology* Aortic Aneurysm, Abdominal / genetics, metabolism, pathology, physiopathology* Blotting, Western Cathepsins / analysis Collagenases / analysis Cytokines / analysis Disease Progression Enzyme-Linked Immunosorbent Assay Female Gene Expression Regulation Humans Inflammation Mediators / analysis Macrophages / pathology Male Middle Aged NF-kappa B / analysis Neutrophil Infiltration Popliteal Artery / chemistry, pathology, physiopathology* RNA, Messenger / analysis Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes, Helper-Inducer / pathology Transcription Factor AP-1 / analysis |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Inflammation Mediators; 0/NF-kappa B; 0/RNA, Messenger; 0/Transcription Factor AP-1; EC 3.4.-/Cathepsins; EC 3.4.24.-/Collagenases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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