Vein graft neointimal hyperplasia is exacerbated by tumor necrosis factor receptor-1 signaling in graft-intrinsic cells.
OBJECTIVE: Vein graft remodeling and neointimal hyperplasia involve inflammation, graft-intrinsic cells, and recruitment of vascular progenitor cells. We sought to examine if the inflammatory cytokine tumor necrosis factor (TNF) affects vein graft remodeling via its p55 TNF receptor-1 (p55). METHODS AND RESULTS: Inferior vena cava-to-carotid artery interposition grafting was performed between p55-/- and congenic (C57Bl/6) wild-type (WT) mice. Immunofluorescence revealed TNF in early (2-week) vein grafts. Six weeks postoperatively, luminal and medial areas were indistinguishable among all vein graft groups. However, neointimal area was reduced in p55-/- grafts: by 40% in p55-/- grafts placed in p55-/- recipients, and by 21% in p55-/- grafts placed in WT recipients, compared with WT grafts in WT recipients (P<0.05). In 2-week-old vein grafts, p55 deficiency reduced intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and monocyte chemoattractant protein-1 expression by 50% to 60%, and increased the extent of graft endothelialization. In vitro, TNF promoted chemokine expression and [3H]thymidine incorporation in vascular smooth muscle cells (SMCs) from WT, but not from p55-/- mice. However, responses of WT and p55-/- SMCs to other growth factors were equivalent. CONCLUSIONS: Signaling via p55, in vein graft-intrinsic cells, contributes to the pathogenesis of vein graft neointimal hyperplasia.
Duke Scholars
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- Vena Cava, Inferior
- Veins
- Tunica Intima
- Tumor Necrosis Factor-alpha
- Signal Transduction
- Receptors, Tumor Necrosis Factor, Type I
- Neovascularization, Pathologic
- Mice, Inbred C57BL
- Mice, Congenic
- Mice
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Vena Cava, Inferior
- Veins
- Tunica Intima
- Tumor Necrosis Factor-alpha
- Signal Transduction
- Receptors, Tumor Necrosis Factor, Type I
- Neovascularization, Pathologic
- Mice, Inbred C57BL
- Mice, Congenic
- Mice