Tenascin-C is an essential factor for neointimal hyperplasia after aortotomy in mice

Yamamoto, Kazuhito; Onoda, Koji; Sawada, Yasuhiro; Fujinaga, Kazuya; Imanaka‐Yoshida, Kyoko; Shimpo, Hideto; Yoshida, Toshimichi; Yada, Isao

doi:10.1016/j.cardiores.2004.10.034

Cited by 41 publications

(51 citation statements)

References 21 publications

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“…Cilostazol inhibited not only PDGF-induced SMC proliferation, but also TNC mRNA expression induced by PDGF in cultured aortic SMCs [17]. We also demonstrated that neointimal formation at suture sites after aortotomy in TNC-deficient mice was noticeably reduced compared to that in wild-type [18]. TNC may be a prime target for therapy in suppressing neointimal hyperplasia after vascular surgery.…”

Section: Introductionmentioning

confidence: 58%

“…Although marked expression of TNC has been found in various vascular lesions in active phases [3,4,6,7], its functional significance during the development of neointimal hyperplasia remains obscure. We recently demonstrated the contribution of TNC to neointimal hyperplasia in a simple aortotomy model using TNCdeficient mice [18]. In this regard, we carried out the present study to elucidate the direct contribution to stenosis of free artery graft transplantation using TNC-deficient mice.…”

Section: Discussionmentioning

confidence: 99%

“…Four cross-sections were selected from the distal anastomotic sites and stained with elastica van Gieson to demarcate the internal elastic lamina. For each section, the ratio between the neointima and the media was calculated using an image analysis system (Adobe Photoshop version 5.0J and NIH Image version 1.61, Macintosh) as previously described [18].…”

Section: Graft Harvesting and Morphometric Analysismentioning

confidence: 99%

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

Sawada

Onoda

Imanaka‐Yoshida

et al. 2007

Cardiovascular Research

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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. 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. 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.

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Section: Introductionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Graft Harvesting and Morphometric Analysismentioning

confidence: 99%

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

Sawada

Onoda

Imanaka‐Yoshida

et al. 2007

Cardiovascular Research

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“…1-4 Following vascular injury, however, ECM-degrading matrix metalloproteinases (MMPs) remodel the preexisting ECM to create a tissue microenvironment that is conducive for SMC proliferation, migration, and survival. [3][4][5] Understanding how alterations in adhesive interactions within the vascular ECM modify SMC behavior, therefore, represents an important question in vascular pathobiology.Tenascin-C (TN-C) is an ECM glycoprotein induced within remodeling hypertensive pulmonary arteries (PAs), 6 -10 as well as in systemic, obliterative vasculopathies, [11][12][13] where it supports vascular SMC proliferation, migration, and survival. 4,14,15 In keeping with the idea that TN-C plays a direct role in promoting vascular disease, studies using TN-C null mice demonstrate that these animals are refractory to neointimal hyperplasia after aortotomy.…”

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confidence: 99%

ROCK Controls Matrix Synthesis in Vascular Smooth Muscle Cells

Chapados

Abe

Ihida-Stansbury

et al. 2006

Circulation Research

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Abstract-Tenascin-C (TN-C) is an extracellular matrix (ECM) protein expressed within remodeling systemic and pulmonary arteries (PAs), where it supports vascular smooth muscle cell (SMC) proliferation. Previously, we showed that A10 SMCs cultivated on native type I collagen possess a spindle-shaped morphology and do not express TN-C, whereas those on denatured collagen possess a well-defined F-actin stress fiber network, a spread morphology, and they do express TN-C. To determine whether changes in cytoskeletal architecture control TN-C, SMCs on denatured collagen were treated with cytochalasin D, which decreased SMC spreading and activation of extracellular signal-regulated kinase 1/2 (ERK1/2), signaling effectors required for TN-C transcription. Next, to determine whether cell shape, dictated by the F-actin cytoskeleton, regulates TN-C, different geometries of SMCs (ranging from spread to round) were engineered on denatured collagen: as SMCs progressively rounded, ERK1/2 activity and TN-C transcription declined. Because RhoA and Rho kinase (ROCK) regulate cell morphology by controlling cytoskeletal architecture, we reasoned that these factors might also regulate TN-C. Indeed, SMCs on denatured collagen possessed higher levels of RhoA activity than those on native collagen, and blocking RhoA or ROCK activities attenuated SMC spreading, ERK1/2 activity, and TN-C expression in SMCs on denatured collagen. Thus, ROCK controls the configuration of the F-actin cytoskeleton and SMC shape in a manner that is permissive for ERK1/2-dependent production of TN-C. Finally, we showed that inhibition of ROCK activity suppresses SMC TN-C expression and disease progression in hypertensive rat PAs. Thus, in addition to its role in regulating vasoconstriction, ROCK also controls matrix production. (Circ Res. 2006;99:837-844.)Key Words: tenascin-C Ⅲ smooth muscle Ⅲ ROCK Ⅲ pulmonary hypertension A dult vascular smooth muscle cells (SMCs) reside within a type I collagen-enriched extracellular matrix (ECM) that helps to maintain the majority of these cells in a nonmotile, growth-arrested, and differentiated state. 1-4 Following vascular injury, however, ECM-degrading matrix metalloproteinases (MMPs) remodel the preexisting ECM to create a tissue microenvironment that is conducive for SMC proliferation, migration, and survival. [3][4][5] Understanding how alterations in adhesive interactions within the vascular ECM modify SMC behavior, therefore, represents an important question in vascular pathobiology.Tenascin-C (TN-C) is an ECM glycoprotein induced within remodeling hypertensive pulmonary arteries (PAs), 6 -10 as well as in systemic, obliterative vasculopathies, [11][12][13] where it supports vascular SMC proliferation, migration, and survival. 4,14,15 In keeping with the idea that TN-C plays a direct role in promoting vascular disease, studies using TN-C null mice demonstrate that these animals are refractory to neointimal hyperplasia after aortotomy. 11 Further, blocking TN-C expression in cultured hypertensive rat PAs induces ...

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“…94 The involvement of TN-C in the intimal hyperplasia of occlusive/stenotic vascular disease has also been extensively studied. Intimal hyperplasia is defined as excessive migration and proliferation of SMCs 22 Therefore, TN-C may be a target molecule for controlling stenotic neointimal formation. Recent drug-eluting stents have remarkably reduced the rate of restenosis and, at the same time, have created a need for more precise evaluation of pathological change of the lesion combined with vascular imaging.…”

Section: Tn-c In the Vascular Systemmentioning

confidence: 99%

Tenascin-C in Cardiovascular Tissue Remodeling

Imanaka‐Yoshida

2012

Circ J

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Tenascin-C is an essential factor for neointimal hyperplasia after aortotomy in mice

Abstract: We have presented direct evidence that tenascin-C is a crucial molecule in neointimal hyperplasia at anastomotic sites.

Cited by 41 publications

References 21 publications

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

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

ROCK Controls Matrix Synthesis in Vascular Smooth Muscle Cells

Tenascin-C in Cardiovascular Tissue Remodeling

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