Mechanism of progression of neointimal hyperplasia at the vasada anastomatic strictwe : a study in tenascin-C Deficient Mice

瓦萨达吻合口新生内膜增生的进展机制：腱蛋白-C缺陷小鼠的研究

• 批准号: 14370409
• 负责人: ONODA Koji
• 金额: $ 3.78万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370409/
• 关键词: Tenascin-C; Vasculai grafto stricture; extracellular matrix; intimal hyperplasia; antery graft stenosis; immuno histochemistry; Knock-out mouse

A simple aortotomy model was constructed using mice. In the wild-type mice, neointimal hyperplasia was observed at the suture sites at days 14 and 28. Immunohistochemical staining showed the strong expression of tenascin-C in both the neoinitima and media around the suture line at day 14. At day 28, tenascin-C staining was detected in the neointima, but not in the media. In the tenascin-C-deficient mice, much less neointimal hyperplasia was seen compared to in the wild-type mice and the mean neointima/media area ratio decreased to 45.4% and 30.5% at days 14 and 28, respectively. Proliferating cell nuclear antigen indeces in the wild-type mice were two times higher than those in the tenascin-C-deficient mice at day 14. Less alcian blue-positive proteoglycans were deposited in the neointima of the tenascin-C-deficient mice than the wild-type mice. These results suggest that tenascin-C promotes neointimal cell migration and proliferation, and deposition of proteoglycans. The current study provide direct evidence that tenascin-C is a key molecule in neointimal hyperplasia in anastomotic stenosis, implying its role as a target molecule for the prevention of stenosis.

使用小鼠构建了简单的主动脉切开术模型。在野生型小鼠中，第14天和第28天在缝合部位观察到新生内膜增生。免疫组织化学染色显示第14天缝合线周围的新内膜和中膜中生腱蛋白-C强烈表达。第28天，在新内膜中检测到生腱蛋白-C染色，但在中膜中未检测到。在生腱蛋白-C 缺陷小鼠中，与野生型小鼠相比，新内膜增生要少得多，并且平均新内膜/中膜面积比在第 14 天和第 28 天分别下降至 45.4% 和 30.5%。第14天时，野生型小鼠的增殖细胞核抗原比生腱蛋白-C缺陷型小鼠高两倍。腱生蛋白-C缺陷型小鼠的新内膜中沉积的阿尔新蓝阳性蛋白多糖比野生型小鼠少。这些结果表明生腱蛋白-C 促进新内膜细胞迁移和增殖以及蛋白聚糖的沉积。目前的研究提供了直接证据表明生腱蛋白-C是吻合口狭窄新生内膜增生的关键分子，这意味着其作为预防狭窄的靶分子的作用。

项目成果

Ming Cai, et al.: "Degradation of Tenascin-C and Activity of Matrix Metalloproteinase -2 are Associated with Tunor Recarreuce in Early Stage Non-Small Cell Lung Cancer."Clinical Cancer Res.. 8. 1152-1156 (2002)

Ming Cai 等人：“腱蛋白-C 的降解和基质金属蛋白酶 -2 的活性与早期非小细胞肺癌中的肿瘤复发相关。”临床癌症研究 8. 1152-1156 (2002)

Kazuya Fujinaga, et al.: "Locally applied alostazol sappresses necintomal hyperplasia by inhibiting tenascin-C synthesis and smooth muscle cell preliferation in free astery grafo"J.Thorac.Cardiovar.Sorg.. in press. (2004)

Kazuya Fujinaga 等人：“局部应用阿洛他唑通过抑制游离 astery grafo 中生腱蛋白-C 合成和平滑肌细胞增殖来抑制坏死瘤增生”J.Thorac.Cardiovar.Sorg.. 正在出版。

Kazuya Fujinaga: "Locally applied cilostazol suppresses neointimal hyperplasia by inhibiting tenascin-C synthesis and smooth muscle cell proliferation in free artery grafts"J.Thorac.Cardiovasc.Surg.. (In press). (2004)

Kazuya Fujinaga：“局部应用西洛他唑通过抑制游离动脉移植物中生腱蛋白-C 合成和平滑肌细胞增殖来抑制新内膜增生”J.Thorac.Cardiovasc.Surg.（正在出版）。

Ming Cai: "Degradation of Tenascin-C and Activity of Matrix Metalloproteinase-2 Are Associated with Tumor Recurrence in Early Stage Non-Small Cell Lung Cancer."Clinical Cancer Research. 8. 1152-1156 (2002)

蔡明：“腱蛋白-C 的降解和基质金属蛋白酶-2 的活性与早期非小细胞肺癌的肿瘤复发有关。”临床癌症研究。

Kazuya Fujinaga: "Locally applied cilostazol suppresses neointimal hyperplasia by inhibiting tenascin-C synthesis and smooth muscle cell proliferation in free artery grafts."J.Thorac.Cardiovasc.Surg.. (in press). (2004)

Kazuya Fujinaga：“局部应用西洛他唑通过抑制游离动脉移植物中生腱蛋白-C 的合成和平滑肌细胞增殖来抑制新内膜增生。”J.Thorac.Cardiovasc.Surg.（出版中）。