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Background

The uptake of oxidized low-density lipoprotein (OxLDL) by macrophage scavenger receptors is thought to be a key process in the formation of foam cells, the hallmark of early atherosclerotic lesions. CXCL16/scavenger receptor for phosphatidylserine and OxLDL is a multifunctional chemokine that exhibits scavenger receptor activity toward oxidized lipids in a membrane-bound configuration and may be shed to serve as a chemoattractant for T helper 1-polarized T lymphocytes. These properties, as well as the expression of CXCL16 in human and mouse atheroma, suggest that CXCL16 plays a role in atherosclerosis.

Methods and results

To examine the role of CXCL16 in plaque formation, we created CXCL16-deficient mice (CXCL16-/-) and bred them with mice deficient in the LDL receptor (LDLR-/-). In vitro, macrophages from CXCL16-/-mice have a significant reduction in the capacity to bind and internalize OxLDL. We found that CXCL16-/-/LDLR-/-mice have accelerated atherosclerosis, enhanced macrophage recruitment to the aortic arch, and more abundant mRNA for monocyte chemotactic protein-1 and tumor necrosis factor-alpha.

Conclusions

These data suggest that scavenger receptor activity mediated by CXCL16 in vivo is atheroprotective, and they contrast with studies that document protection from atherosclerosis in scavenger receptor class A- and CD36-deficient mice."xsd:string
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http://purl.uniprot.org/citations/16880330http://purl.uniprot.org/core/author"Charo I.F."xsd:string
http://purl.uniprot.org/citations/16880330http://purl.uniprot.org/core/author"Aslanian A.M."xsd:string
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http://purl.uniprot.org/citations/16880330http://purl.uniprot.org/core/title"Targeted disruption of the scavenger receptor and chemokine CXCL16 accelerates atherosclerosis."xsd:string
http://purl.uniprot.org/citations/16880330http://purl.uniprot.org/core/volume"114"xsd:string
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