Vein Graft Neointimal Hyperplasia Is Exacerbated by Tumor Necrosis Factor Receptor-1 Signaling in Graft-Intrinsic Cells

Lisheng Zhang, Karsten Peppel, Leigh Brian, Lynn Chien, Neil J. Freedman
2004 Arteriosclerosis, Thrombosis and Vascular Biology  
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 Ϫ/Ϫ and congenic (C57Bl/6) wild-type (WT) mice. Immunofluorescence revealed TNF in early (2- week)
more » ... 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 Ϫ/Ϫ grafts: by 40% in p55 Ϫ/Ϫ grafts placed in p55 Ϫ/Ϫ recipients, and by 21% in p55 Ϫ/Ϫ grafts placed in WT recipients, compared with WT grafts in WT recipients (PϽ0.05). 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 [ 3 H]thymidine incorporation in vascular smooth muscle cells (SMCs) from WT, but not from p55 Ϫ/Ϫ mice. However, responses of WT and p55 Ϫ/Ϫ 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. (Arterioscler Thromb Vasc Biol. 2004;24:2277-2283.)
doi:10.1161/01.atv.0000147766.68987.0d pmid:15486311 fatcat:vr4264nbgva3zjt7wuia7skrdq