Document Detail

Differential influence of chemokine receptors CCR2 and CXCR3 in development of atherosclerosis in vivo.
MedLine Citation:
PMID:  16061736     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Recruitment of mononuclear leukocytes within atherosclerotic lesions is a critical step in atherogenesis. Mice lacking the chemokine receptor CCR2, highly expressed on macrophages but also on T lymphocytes, show a striking reduction of atherosclerotic lesion formation. The chemokine receptor CXCR3 is a marker of activated T helper type 1 lymphocytes, the principal T lymphocyte type detected within atheroma. We investigated whether the deletion of both of these 2 important receptors expressed on the principal inflammatory cells present in atheroma would further affect atherogenesis in vivo. METHODS AND RESULTS: We crossed ApoE(-/-) mice with either CCR2(-/-) or CXCR3- mice and crossed ApoE(-/-) CCR2(-/-) mice with the ApoE(-/-) CXCR3- mice to generate a triple knockout strain. Analysis of atherosclerosis development after 10 weeks of high-cholesterol diet revealed differential effects on early atherosclerotic lesions in the abdominal aorta and on advanced lesions in aortic roots. ApoE(-/-) CXCR3- mice, but not the triple knockout mice, displayed significantly reduced atherosclerotic lesion development within abdominal aortas compared with ApoE(-/-) CCR2(-/-) and ApoE(-/-) mice. This reduction of lesion formation correlated with an upregulation of antiinflammatory molecules such as interleukin-10, interleukin-18BP, and endothelial nitric oxide synthase and with an increased number of regulatory T lymphocytes within atherosclerotic lesions. In contrast, lesion size development within the aortic roots was more enhanced in ApoE(-/-) and ApoE(-/-) CXCR3- mice compared with ApoE(-/-) CCR2(-/-) and triple knockout mice. CONCLUSIONS: Blocking chemokine signaling in vivo through deletion of the chemokine receptors CCR2 and CXCR3 has differential effects during atherogenesis. In addition, our results point to an important role of regulatory T lymphocytes during early atherogenesis.
Niels R Veillard; Sabine Steffens; Graziano Pelli; B Lu; Brenda R Kwak; Craig Gerard; Israel F Charo; François Mach
Related Documents :
23337926 - Low-level laser reduces the production of tnf-α, ifn-γ, and il-10 induced by ova.
11809756 - Loss of lymphotoxin-alpha but not tumor necrosis factor-alpha reduces atherosclerosis i...
20939036 - Cumulative effects of hypercholesterolemia on tendon biomechanics in a mouse model.
17431486 - Cardiovascular effects of pulmonary exposure to single-wall carbon nanotubes.
10795756 - Cytokine production by capan-1 and capan-2 cell lines.
21961576 - The evolving experience with therapeutic tnf inhibition in sepsis: considering the pote...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2005-08-01
Journal Detail:
Title:  Circulation     Volume:  112     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-08-09     Completed Date:  2006-02-14     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  870-8     Citation Subset:  AIM; IM    
Division of Cardiology, Foundation for Medical Research, University Hospital Geneva, Geneva, Switzerland.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Apolipoproteins E / deficiency
Atherosclerosis / genetics*,  pathology
Base Sequence
Crosses, Genetic
DNA Primers
Disease Models, Animal
Mice, Inbred C57BL
Mice, Knockout
Receptors, CCR2
Receptors, CXCR3
Receptors, Chemokine / deficiency,  genetics*,  metabolism
Grant Support
Reg. No./Substance:
0/Apolipoproteins E; 0/Ccr2 protein, mouse; 0/Cxcr3 protein, mouse; 0/DNA Primers; 0/Receptors, CCR2; 0/Receptors, CXCR3; 0/Receptors, Chemokine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Exercise intolerance in adult congenital heart disease: comparative severity, correlates, and progno...
Next Document:  Tobacco smoke exposure is associated with the metabolic syndrome in adolescents.