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

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 24; no. 12; pp. 2277 - 2283
• Main Authors: Zhang, Lisheng, Peppel, Karsten, Brian, Leigh, Chien, Lynn, Freedman, Neil J
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.12.2004; Hagerstown, MD Lippincott
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Animals; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Carotid Artery, Common - surgery; Cell Adhesion Molecules - biosynthesis; Cell Line; Chemokine CCL2 - biosynthesis; Chemokines - biosynthesis; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Enzyme Activation - physiology; Hyperplasia - enzymology; Hyperplasia - genetics; Hyperplasia - pathology; Male; Medical sciences; Mice; Mice, Congenic; Mice, Inbred C57BL; Neovascularization, Pathologic - enzymology; Neovascularization, Pathologic - metabolism; Receptors, Tumor Necrosis Factor, Type I - deficiency; Receptors, Tumor Necrosis Factor, Type I - metabolism; Receptors, Tumor Necrosis Factor, Type I - physiology; Signal Transduction - physiology; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Tumor Necrosis Factor-alpha - biosynthesis; Tunica Intima - chemistry; Tunica Intima - enzymology; Tunica Intima - metabolism; Tunica Intima - pathology; Veins - enzymology; Veins - metabolism; Veins - transplantation; Vena Cava, Inferior - cytology; Vena Cava, Inferior - transplantation; mouse models; Hyperplasia; Cytokine; Rodentia; Cardiovascular disease; Smooth muscle; Inflammation; Vascular disease; Vascular remodeling; smooth muscle cells; Vertebrata; Mammalia; Mouse; Tumor necrosis factor; Animal; Atherosclerosis
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.ATV.0000147766.68987.0d

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 graftsby 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 [H]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.