| First Author | Aslanian AM | Year | 2006 |
| Journal | Circulation | Volume | 114 |
| Issue | 6 | Pages | 583-90 |
| PubMed ID | 16880330 | Mgi Jnum | J:123851 |
| Mgi Id | MGI:3719761 | Doi | 10.1161/CIRCULATIONAHA.105.540583 |
| Citation | Aslanian AM, et al. (2006) Targeted disruption of the scavenger receptor and chemokine CXCL16 accelerates atherosclerosis. Circulation 114(6):583-90 |
| abstractText | 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. |
