Tenascin-C synthesized in both donor grafts and recipients accelerates artery graft stenosis.
OBJECTIVE
Tenascin-C, an extracellular matrix glycoprotein, is thought to play an important role in neointimal hyperplasia of artery bypass grafts. In this study, the direct contribution of tenascin-C to neointimal hyperplasia of free artery grafts and the origin of tenascin-C-producing cells were examined using tenascin-C transgenic mice.


RESULTS
Abdominal aorta-to-carotid artery interposition grafting was performed in mice. When grafts from wild-type mice were transplanted to wild-type, neointimal hyperplasia was observed in the grafts at days 14 and 28. Immunohistochemical staining showed strong expression of tenascin-C in the media and neointima of the grafts. Much less neointimal hyperplasia was seen when grafts from tenascin-C-deficient mice were transplanted to tenascin-C-deficient mice. In tenascin-C-deficient grafts transplanted to wild-type mice, tenascin-C deposition was observed only in the neointima. In the reverse combination, deposition was seen in the media and neointima. The source of the tenascin-C-producing cells was analyzed using heterozygous mice that identically express both tenascin-C and LacZ. While LacZ-positive cells were seen only in the neointima of artery grafts from wild-type transplanted to mutant mice, positive cells were detected in both the neointima and media in grafts from mutant to wild-type mice.


CONCLUSIONS
We presented direct evidence that tenascin-C is a crucial molecule in neointimal hyperplasia in free artery grafts, and that tenascin-C-producing cells are derived from both donor grafts and recipients.
Sawada
Yasuhiro
Y
Department of Thoracic and Cardiovascular Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
Onoda
Koji
K
Imanaka-Yoshida
Kyoko
K
Maruyama
Junko
J
Yamamoto
Kiyohito
K
Yoshida
Toshimichi
T
Shimpo
Hideto
H
D000714:Anastomosis, Surgical; D000818:Animals; D001011:Aorta / Q000473:pathology / Q000637:transplantation*; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D017536:Carotid Artery, Common / Q000473:pathology / Q000601:surgery; D002465:Cell Movement; D049109:Cell Proliferation; D006083:Graft Occlusion, Vascular / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D006579:Heterozygote; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007763:Lac Operon; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D019063:Tenascin / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*
D019063:Tenascin