| First Author | Hiroyasu S | Year | 2013 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 33 |
| Issue | 1 | Pages | 87-95 |
| PubMed ID | 23117661 | Mgi Jnum | J:216916 |
| Mgi Id | MGI:5609933 | Doi | 10.1161/ATVBAHA.112.300264 |
| Citation | Hiroyasu S, et al. (2013) Donor and recipient cell surface colony stimulating factor-1 promote neointimal formation in transplant-associated arteriosclerosis. Arterioscler Thromb Vasc Biol 33(1):87-95 |
| abstractText | OBJECTIVE: Transplant-associated arteriosclerosis manifests as progressive vascular neointimal expansion throughout the arterial system of allografted solid organs, and eventually compromises graft perfusion and function. Allografts placed in colony stimulating factor (CSF)-1-deficient osteopetrotic (Csf1(op)/Csf1(op)) mice develop very little neointima, a finding attributed to impaired recipient macrophage function. We examined how CSF-1 affects neointima-derived vascular smooth muscle cells, tested the significance of CSF-1 expressed in donor tissue, and evaluated the contribution of secreted versus cell surface CSF-1 isoforms in transplant-associated arteriosclerosis. METHODS AND RESULTS: CSF-1 activated specific signaling pathways to promote migration, survival, and proliferation of cultured vascular smooth muscle cells. Tumor necrosis factor-alpha addition increased CSF-1 and CSF-1 receptor expression, and tumor necrosis factor-alpha-driven proliferation was blocked by anti-CSF-1 antibody. In a mouse vascular allograft model, lack of recipient or donor CSF-1 impaired neointima formation; the latter suggests local CSF-1 function within the allograft. Moreover, reconstitution of donor or recipient cell surface CSF-1, without secreted CSF-1, restored neointimal formation. CONCLUSIONS: Vascular smooth muscle cells activation, including that mediated by tumor necrosis factor-alpha, can be driven in an autocrine/juxtacrine manner by CSF-1. These studies provide evidence for local function of CSF-1 in neointimal expansion, and identify CSF-1 signaling in vascular smooth muscle cells, particularly cell surface CSF-1 signaling, as a target for therapeutic strategies in transplant-associated arteriosclerosis. |
