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Donor and recipient cell surface colony stimulating factor-1 promote neointimal formation in transplant-associated arteriosclerosis.

ABSTRACT: 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.CSF-1 activated specific signaling pathways to promote migration, survival, and proliferation of cultured vascular smooth muscle cells. Tumor necrosis factor-? addition increased CSF-1 and CSF-1 receptor expression, and tumor necrosis factor-?-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.Vascular smooth muscle cells activation, including that mediated by tumor necrosis factor-?, 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.

SUBMITTER: Hiroyasu S

PROVIDER: S-EPMC3524392 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Donor and recipient cell surface colony stimulating factor-1 promote neointimal formation in transplant-associated arteriosclerosis.

Hiroyasu Shungo S Chinnasamy Prameladevi P Hou Rong R Hotchkiss Kylie K Casimiro Isabel I Dai Xu-Ming XM Stanley E Richard ER Sibinga Nicholas E S NE

Arteriosclerosis, thrombosis, and vascular biology 20121101 1

<h4>Objective</h4>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 c ...[more]

PMID: 23117661

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Donor and recipient cell surface colony stimulating factor-1 promote neointimal formation in transplant-associated arteriosclerosis.

Publications

Donor and recipient cell surface colony stimulating factor-1 promote neointimal formation in transplant-associated arteriosclerosis.

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