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- Title
Tenascin-C is an essential factor for neointimal hyperplasia after aortotomy in mice
- Authors
Yamamoto, Kiyohito; Onoda, Koji; Sawada, Yasuhiro; Fujinaga, Kazuya; Imanaka-Yoshida, Kyoko; Shimpo, Hideto; Yoshida, Toshimichi; Yada, Isao
- Abstract
Abstract: 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. Methods and 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.
- Subjects
HYPERPLASIA; EXTRACELLULAR matrix proteins; AORTA surgery; GLYCOPROTEINS
- Publication
Cardiovascular Research, 2005, Vol 65, Issue 3, p737
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1016/j.cardiores.2004.10.034