| First Author | Shaposhnik Z | Year | 2010 |
| Journal | J Lipid Res | Volume | 51 |
| Issue | 7 | Pages | 1962-70 |
| PubMed ID | 20194110 | Mgi Jnum | J:162834 |
| Mgi Id | MGI:4819941 | Doi | 10.1194/jlr.M005215 |
| Citation | Shaposhnik Z, et al. (2010) Arterial colony stimulating factor-1 influences atherosclerotic lesions by regulating monocyte migration and apoptosis. J Lipid Res 51(7):1962-70 |
| abstractText | Previous studies have shown that colony stimulating factor-1 (CSF-1) deficiency dramatically reduced atherogenesis in mice. In this report we investigate this mechanism and explore a therapeutic avenue based on inhibition of CSF-1 signaling. Lesions from macrophage colony stimulating factor-1 (Csf1)+/- mice showed increased numbers of apoptotic macrophages, decreased overall macrophage content, and inflammation. In vitro studies indicated that CSF-1 is chemotactic for monocytes. Bone marrow transplantation studies suggested that vascular cell-derived, rather than macrophage-derived, CSF-1 is responsible for the effect on atherosclerosis. Consistent with previous studies, CSF-1 affected lesion development in a dose-dependent manner, suggesting that pharmacological inhibition of CSF-1 might achieve similar results. Indeed, we observed that treatment of hyperlipidemic mice with a CSF-1 receptor kinase inhibitor inhibited plaque progression. This observation was accompanied by a reduction in the expression of adhesion factors (ICAM-1), macrophage markers (F4/80), inflammatory cytokines (Il-6, Il-1beta), and macrophage matrix degradation enzymes (MMP-9). We conclude that the M-CSF pathway contributes to monocyte recruitment and macrophage survival and that this pathway is a potential target for therapeutic intervention. |
