title: 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.
abstract: 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.affiliation: Department of Surgery, Stanford University, Palo Alto, CA, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Gallo
authors.forename: Ahmad
authors.initials: A
authors.lastname: Saad
authors.forename: Rahmat
authors.initials: R
authors.lastname: Ali
authors.forename: Alan
authors.initials: A
authors.lastname: Dardik
authors.forename: George
authors.initials: G
authors.lastname: Tellides
authors.forename: Arnar
authors.initials: A
authors.lastname: Geirsson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000783:Aneurysm / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D000818:Animals; D017545:Aortic Aneurysm, Thoracic / Q000097:blood* / Q000276:immunology / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002122:Calcium Chloride; D002340:Carotid Artery Diseases / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control; D016022:Case-Control Studies; D054357:Chemokine CXCL10 / Q000097:blood*; D054371:Chemokine CXCL11 / Q000097:blood*; D054370:Chemokine CXCL9 / Q000097:blood*; D016009:Chi-Square Distribution; D003237:Connecticut; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D054367:Receptors, CXCR3 / Q000097:blood* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; C515188:Cxcr3 protein, mouse; D008024:Ligands; D054367:Receptors, CXCR3; D007371:Interferon-gamma; D002122:Calcium Chloride