Tenascin-C synthesized in both donor grafts and recipients accelerates artery graft stenosis

• Published in: Cardiovascular research Vol. 74; no. 3; pp. 366 - 376
• Main Authors: SAWADA, Yasuhiro, ONODA, Koji, IMANAKA-YOSHIDA, Kyoko, MARUYAMA, Junko, YAMAMOTO, Kiyohito, YOSHIDA, Toshimichi, SHIMPO, Hideto
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.06.2007
• Subjects: Anastomosis, Surgical; Animals; Aorta - pathology; Aorta - transplantation; Atherosclerosis - metabolism; Atherosclerosis - pathology; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Carotid Artery, Common - pathology; Carotid Artery, Common - surgery; Cell Movement; Cell Proliferation; Coronary heart disease; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Graft Occlusion, Vascular - etiology; Graft Occlusion, Vascular - metabolism; Graft Occlusion, Vascular - pathology; Heart; Heterozygote; Image Processing, Computer-Assisted; Immunohistochemistry; Lac Operon; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Transgenic; Models, Animal; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Tenascin - analysis; Tenascin - genetics; Tenascin - physiology; Transplantation, Homologous; Tunica Intima - metabolism; Tunica Intima - pathology; Human; Tenascin; Animal model; Transgenic animal; Cardiovascular disease; Cardiovascular surgery; Remodeling; Coronary heart disease; Phlebology; Coronary disease; Transgenic animal models; Artery stenosis; Arterial disease; Vascular disease; Vascular remodeling; Treatment; Donor; Surgery; Graft; Extracellular matrix; Circulatory system; Cardiology
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/j.cardiores.2007.02.028

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. 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. 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.