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. Methods and 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. Immumohistochemical 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. (C) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.