Genetic deletion of chemokine receptor Ccr6 decreases atherogenesis in ApoE-deficient mice.
Circ Res
; 109(4): 374-81, 2011 Aug 05.
Article
em En
| MEDLINE
| ID: mdl-21680896
ABSTRACT
RATIONALE The chemokine receptor Ccr6 is a G-protein-coupled receptor expressed on various types of leukocytes identified in mouse atherosclerotic lesions. Recent evidence suggests that both CCR6 and its ligand CCL20 are also present in human atheroma; however, their functional roles in atherogenesis remain undefined. OBJECTIVE:
Our objective was to delineate the role of Ccr6 in atherogenesis in the apolipoprotein E-deficient (ApoE(-/-)) mouse model of atherosclerosis. METHODS ANDRESULTS:
Both Ccr6 and Ccl20 are expressed in atherosclerotic aorta from ApoE(-/-) mice. Aortic lesion area in Ccr6(-/-)ApoE(-/-) mice was â¼40% and â¼30% smaller than in Ccr6(+/+)ApoE(-/-) mice at 16 and 24 weeks of age, respectively. Transplantation of bone marrow from Ccr6(-/-) mice into ApoE(-/-) mice resulted in â¼40% less atherosclerotic lesion area than for bone marrow from Ccr6(+/+) mice; lesions in Ccr6(-/-)ApoE(-/-) mice had 44% less macrophage content than lesions in Ccr6(+/+)ApoE(-/-) mice. Ccr6 was expressed on a subset of primary mouse monocytes. Accordingly, Ccl20 induced chemotaxis of primary monocytes from wild-type but not Ccr6(-/-) mice; moreover, Ccl20 induced monocytosis in ApoE(-/-) mice in vivo. Consistent with this, we observed 30% fewer monocytes in circulating blood of Ccr6(-/-)ApoE(-/-) mice, mainly because of fewer CD11b(+)Ly6C(high) inflammatory monocytes.CONCLUSIONS:
Ccr6 promotes atherosclerosis in ApoE-deficient mice, which may be due in part to Ccr6 support of normal monocyte levels in blood, as well as direct Ccr6-dependent monocyte migration.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aorta
/
Doenças da Aorta
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Apolipoproteínas E
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Deleção de Genes
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Aterosclerose
/
Receptores CCR6
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article