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

Shungo Hiroyasu, Prameladevi Chinnasamy, Rong Hou, Kylie Hotchkiss, Isabel Casimiro, Xu Ming Dai, E. Richard Stanley, Nicholas E.S. Sibinga

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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 (Csf1op/Csf1op) 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-α addition increased CSF-1 and CSF-1 receptor expression, and tumor necrosis factor-α-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. Conclusion-Vascular smooth muscle cells activation, including that mediated by tumor necrosis factor-α, 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.

Original languageEnglish (US)
Pages (from-to)87-95
Number of pages9
JournalArteriosclerosis, thrombosis, and vascular biology
Volume33
Issue number1
DOIs
StatePublished - Jan 1 2013

Keywords

  • allograft
  • arteriosclerosis
  • chronic rejection
  • macrophage-colony stimulating factor
  • vasculopathy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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