Protective role of CXC receptor 4/CXC ligand 12 unveils the importance of neutrophils in atherosclerosis.
Circ Res
; 102(2): 209-17, 2008 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-17991882
ABSTRACT
The CXC ligand (CXCL)12/CXC receptor (CXCR)4 chemokine-receptor axis controls hematopoiesis, organ development, and angiogenesis, but its role in the inflammatory pathogenesis of atherosclerosis is unknown. Here we show that interference with Cxcl12/Cxcr4 by a small-molecule antagonist, genetic Cxcr4 deficiency, or lentiviral transduction with Cxcr4 degrakine in bone marrow chimeras aggravated diet-induced atherosclerosis in apolipoprotein E-deficient (Apoe-/-) or LDL receptor-deficient (Ldlr-/-) mice. Chronic blockade of Cxcr4 caused leukocytosis and an expansion of neutrophils and increased neutrophil content in plaques, associated with apoptosis and a proinflammatory phenotype. Whereas circulating neutrophils were recruited to atherosclerotic lesions, depletion of neutrophils reduced plaque formation and prevented its exacerbation after blocking Cxcr4. Disrupting Cxcl12/Cxcr4 thus promotes lesion formation through deranged neutrophil homeostasis, indicating that Cxcl12/Cxcr4 controls the important contribution of neutrophils to atherogenesis in mice.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores CXCR4
/
Aterosclerose
/
Quimiocina CXCL12
/
Neutrófilos
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article