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Circulating interferon-γ-inducible Cys-X-Cys chemokine receptor 3 ligands are elevated in humans with aortic aneurysms and Cys-X-Cys chemokine receptor 3 is necessary for aneurysm formation in mice.
MedLine Citation:
PMID:  21962843     Owner:  NLM     Status:  Publisher    
OBJECTIVE: Inflammation is associated with the formation of aortic aneurysm. This study investigates the role of inducible Cys-X-Cys chemokine receptor 3 and its ligands in the pathogenesis of arterial aneurysms. METHODS: Plasma samples from patients with or without a diagnosis of thoracic aortic aneurysms were analyzed by enzyme-linked immunosorbent assay for the T-helper 1 cytokine interferon-γ and the interferon-γ-inducible chemokine receptor 3 ligands: interferon-inducible protein-10, interferon-inducible T-cell alpha chemoattractant, and monokine induced by interferon gamma. Patient charts were reviewed for demographics, initial aortic diameter, and growth rates. Aneurysm diameter and growth rates were correlated with plasma cytokine and chemokine levels using linear regression analysis. We used an animal model of aneurysm formation, where calcium chloride is applied topically to the carotid arteries of wild-type and Cys-X-Cys chemokine receptor 3(-/-) mice. After 10 weeks, the arteries were harvested and analyzed by histology and immunohistochemistry. RESULTS: Patients with thoracic aortic aneurysms had significant elevations in circulating interferon-γ, interferon-inducible protein-10, interferon-inducible T-cell alpha chemoattractant, and monokine induced by interferon gamma compared with referent patients (P < .001). Cytokine and chemokine plasma levels did not correlate with aneurysm size or growth rates. Cys-X-Cys chemokine receptor 3(-/-) mice were protected from aneurysm formation and showed decreased vascular infiltration by CD45(+) leukocytes. CONCLUSION: Elevated plasma levels of interferon-γ and Cys-X-Cys chemokine receptor 3-binding chemokines are present in patients with thoracic aortic aneurysms. The Cys-X-Cys chemokine receptor 3 receptor is necessary for vascular inflammation and the formation of arterial aneurysms in mice.
Amy Gallo; Ahmad Saad; Rahmat Ali; Alan Dardik; George Tellides; Arnar Geirsson
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-28
Journal Detail:
Title:  The Journal of thoracic and cardiovascular surgery     Volume:  -     ISSN:  1097-685X     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-10-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376343     Medline TA:  J Thorac Cardiovasc Surg     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
Department of Surgery, Stanford University, Palo Alto, Calif.
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