Document Detail


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:  MEDLINE    
Abstract/OtherAbstract:
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.
CONCLUSIONS: 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.
Authors:
Amy Gallo; Ahmad Saad; Rahmat Ali; Alan Dardik; George Tellides; Arnar Geirsson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-09-29
Journal Detail:
Title:  The Journal of thoracic and cardiovascular surgery     Volume:  143     ISSN:  1097-685X     ISO Abbreviation:  J. Thorac. Cardiovasc. Surg.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-02-20     Completed Date:  2012-04-04     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  0376343     Medline TA:  J Thorac Cardiovasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  704-10     Citation Subset:  AIM; IM    
Copyright Information:
Published by Mosby, Inc.
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Analysis of Variance
Aneurysm / chemically induced,  genetics,  immunology,  metabolism*,  prevention & control
Animals
Aortic Aneurysm, Thoracic / blood*,  immunology,  pathology
Biological Markers / blood
Calcium Chloride
Carotid Artery Diseases / chemically induced,  genetics,  immunology,  metabolism*,  prevention & control
Case-Control Studies
Chemokine CXCL10 / blood*
Chemokine CXCL11 / blood*
Chemokine CXCL9 / blood*
Chi-Square Distribution
Connecticut
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Female
Humans
Interferon-gamma / blood*
Ligands
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Receptors, CXCR3 / blood*,  deficiency,  genetics,  metabolism*
Up-Regulation
Grant Support
ID/Acronym/Agency:
P01 HL70295/HL/NHLBI NIH HHS; R01 HL095498/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/CXCL10 protein, human; 0/CXCL11 protein, human; 0/CXCL9 protein, human; 0/CXCR3 protein, human; 0/Chemokine CXCL10; 0/Chemokine CXCL11; 0/Chemokine CXCL9; 0/Cxcr3 protein, mouse; 0/Ligands; 0/Receptors, CXCR3; 82115-62-6/Interferon-gamma; M4I0D6VV5M/Calcium Chloride

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