Copyright © 2004, European Society of Cardiology
Tenascin-C is an essential factor for neointimal hyperplasia after aortotomy in mice
aDepartment of Thoracic and Cardiovascular Surgery, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
bDepartment of Pathology, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
* Corresponding author. Department of Thoracic and Cardiovascular Surgery, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan. Tel.: +81 59 232 1111; fax: +81 59 231 2845. Email address: k-onoda{at}clin.medic.mieu.ac.jp
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.
KEYWORDS Cardiovascular surgery; Coronary disease; Remodeling; Transgenic animal models; Extracellular matrix
Time for primary review 18 days
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