Tenascin-C is an essential factor for neointimal hyperplasia after aortotomy in mice.
OBJECTIVE
Neointimal hyperplasia at the arterial anastomotic site is a critical problem during cardiovascular surgery. It has been suggested that tenascin-C (TN-C), an extracellular matrix (ECM) glycoprotein, might play an important role in neointimal hyperplasia. In this study, the direct contribution of tenascin-C to neointimal hyperplasia after aortotomy was examined using tenascin-C-deficient (TNKO) mice.


RESULTS
A simple aortotomy model was constructed in mice. In wild-type (WT) mice, neointimal hyperplasia was observed at the suture sites at days 14 and 28. Immunohistochemical staining showed strong expression of tenascin-C in both neointima and media around the suture line at day 14. At day 28, tenascin-C staining was detected in neointima, but not in media. In tenascin-C-deficient mice, much less neointimal hyperplasia was seen compared to that in wild-type mice, and the mean neointima/media area ratio decreased to 52.8% and 34.3% at days 14 and 28, respectively. The proliferating cell nuclear antigen indices in wild-type mice were twice those in tenascin-C-deficient mice at day 14. There were fewer Alcian blue-positive proteoglycans deposited in the neointima of tenascin-C-deficient mice than in wild-type mice. These results suggest that tenascin-C promotes neointimal cell migration and proliferation, and the deposition of proteoglycans.


CONCLUSIONS
We have presented direct evidence that tenascin-C is a crucial molecule in neointimal hyperplasia at anastomotic sites.
Yamamoto
Kiyohito
K
Department of Thoracic and Cardiovascular Surgery, Mie University School of Medicine, Tsu, Mie 514-8507, Japan.
Onoda
Koji
K
Sawada
Yasuhiro
Y
Fujinaga
Kazuya
K
Imanaka-Yoshida
Kyoko
K
Shimpo
Hideto
H
Yoshida
Toshimichi
T
Yada
Isao
I
D000199:Actins / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000601:surgery*; D001807:Blood Vessel Prosthesis; D002455:Cell Division; D002465:Cell Movement; D005260:Female; D006083:Graft Occlusion, Vascular / Q000473:pathology / Q000503:physiopathology*; D006965:Hyperplasia; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D013537:Sutures; D019063:Tenascin / Q000378:metabolism / Q000502:physiology*; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*; D017540:Tunica Media / Q000378:metabolism
D000199:Actins; D018809:Proliferating Cell Nuclear Antigen; D019063:Tenascin