Locally applied cilostazol suppresses neointimal hyperplasia by inhibiting tenascin-C synthesis and smooth muscle cell proliferation in free artery grafts

Fujinaga, Kazuya; Onoda, Koji; Yamamoto, Kazuhito; Imanaka‐Yoshida, Kyoko; Takao, Motoshi; Shimono, Takatsugu; Shimpo, Hideto; Yoshida, Toshimichi; Yada, Isao

doi:10.1016/j.jtcvs.2003.11.015

Cited by 36 publications

(32 citation statements)

References 28 publications

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“…In the aortic segments donated by WT mice (WTNWT and WTNTN− groups), the changes in the distribution of TNC expression during the first 28 days after surgery, which seemed to shift from the media to the neointima, were similar to those previously observed in free artery grafts in rats [17]. By contrast, in the grafts donated by TN− mice transplanted to WT mice (TN−NWT group), the expression of TNC protein was detected only in the neointima, and was associated with the emergence of predominant α-SMA positive cells.…”

Section: Discussionsupporting

confidence: 76%

“…Careful observation also suggests that some TNC-producing cells may directly migrate from recipient vessels into the neointima of grafts across the anastomosis. In vascular lesions, several types of cells including SMCs [8,17], fibroblasts [37], myofibroblasts [38], and endothelial cells [39] have been reported to express TNC protein. The double staining of LacZ and α-SMA showed that TNC-producing cells were positive for α-SMA in both the TN+/−NWT and WTNTN+/− groups.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, in a previous study we demonstrated that local administration of cilostazol, a specific inhibitor of cAMP phosphodiesterase III inhibitor, remarkably suppressed neointimal hyperplasia, and was associated with inhibiting TNC expression and cell accumulation in the neointima of free artery grafts of rats [17]. 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].…”

Section: Introductionmentioning

confidence: 92%

“…Rabbit control IgGs were used instead of primary antibodies as negative immunostaining controls. Immunohistochemical staining for proliferating cell nuclear antigen (PCNA), Ki67, and α-SMA was performed using mouse monoclonal antibody against PCNA (PC10, EPOS, DAKO, Tokyo, Japan), monoclonal rat anti-mouse Ki67 (DAKO, Tokyo, Japan), and peroxidase-conjugate anti-α-SMA antibody (EPOS, DAKO, Tokyo Japan), respectively [17]. The PCNA or Ki67 labeling index was determined by dividing the number of PCNA-or Ki67-positive cells, respectively, by the total number of nucleated cells in neointima and media from each section.…”

Section: Immunohistochemistry and Histochemistrymentioning

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: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Section: Immunohistochemistry and Histochemistrymentioning

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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“…Cilostazol inhibits phosphodiesterase III preventing tenascin-C expression by vascular smooth muscle cells during neointimal hyperplasia. 25,26 AT-1 antagonists and ACE inhibitors could also be useful since they inhibit angiotensin II, which is a potent inducer of tenascin-C. These drugs were shown to block vascular tenascin-C expression in hypertensive patients.…”

Section: Blocking Tenascin-c Inducing Signaling With Inhibitory Drugsmentioning

confidence: 99%

Tenascin-C: Exploitation and collateral damage in cancer management

Spenlé

Saupe

Midwood³

et al. 2015

Cell Adhesion & Migration

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Tenascin‐C in Development and Disease of Blood Vessels

Imanaka‐Yoshida

Yoshida

Miyagawa‐Tomita

2014

The Anatomical Record

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Tenascin-C (TNC) is an extracellular glycoprotein categorized as a matricellular protein. It is highly expressed during embryonic development, wound healing, inflammation, and cancer invasion, and has a wide range of effects on cell response in tissue morphogenesis and remodeling including the cardiovascular system. In the heart, TNC is sparsely detected in normal adults but transiently expressed at restricted sites during embryonic development and in response to injury, playing an important role in myocardial remodeling. Although TNC in the vascular system appears more complex than in the heart, the expression of TNC in normal adult blood vessels is generally low. During embryonic development, vascular smooth muscle cells highly express TNC on maturation of the vascular wall, which is controlled in a way that depends on the embryonic site of cell origin. Strong expression of TNC is also linked with several pathological conditions such as cerebral vasospasm, intimal hyperplasia, pulmonary artery hypertension, and aortic aneurysm/ dissection. TNC synthesized by smooth muscle cells in response to developmental and environmental cues regulates cell responses such as proliferation, migration, differentiation, and survival in an autocrine/ paracrine fashion and in a context-dependent manner. Thus, TNC can be a key molecule in controlling cellular activity in adaptation during normal vascular development as well as tissue remodeling in pathological conditions. Anat Rec, 297:1747Rec, 297: -1757Rec, 297: , 2014. V C 2014 Wiley Periodicals, Inc.Key words: muscle; tenascin-C; blood vessel Abbreviations used: ECM 5 extracellular matrix; TNC 5 tenascin-C; VSMC 5 vascular smooth muscle cell; aSMA 5 a-smooth muscle actin; SAH 5 subarachnoid hemorrhage.

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Locally applied cilostazol suppresses neointimal hyperplasia by inhibiting tenascin-C synthesis and smooth muscle cell proliferation in free artery grafts

Abstract: A single topical administration of cilostazol may suppress neointimal hyperplasia by inhibiting cell proliferation and tenascin-C synthesis in free artery grafts, presenting the potential for clinical use in vascular surgery.

Cited by 36 publications

References 28 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

Tenascin-C: Exploitation and collateral damage in cancer management

Tenascin‐C in Development and Disease of Blood Vessels

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