A study for prevention of ventricular remodeling after myocardial infarction by regulating functions of tenascin-C.
| Project/Area Number |
17590724
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Mie University |
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Principal Investigator |
YOSHIDA Kyoko Mie University, Graduate School of Medicine, Department of Pathology and Matrix Biology, Research Professor, 大学院医学系研究科, 助教授 (00242967)
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| Co-Investigator(Kenkyū-buntansha) |
ONISHI Katsuya Mie University, Graduate School of Medicine, Department of Laboroatory Medicine, Assistant Professor, 大学院医学系研究科, 助手 (40343222)
HARA Mari Mie University, Graduate School of Medicine, Department of Pathology and Matrix Biology, Research Associate, 大学院医学系研究科, 教務職員 (30176383)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | tenascin / extracellular matrix / knockout mouse / transgenic mouse / myocardial infarction / ventricular remodeling |
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| Research Abstract |
Tenascin-C (TN-C), an extracellular matrix glycoprotein, transiently appears in the pathologic heart, playing important roles in tissue remodeling. To elucidate its role in ventricular remodeling after acute myocardial infarction(AMI), we measured TN-C levels in patients with AMI and compared with cardiac function and patient outcomes. Serum TN-C levels were significantly elevated during the acute stage after AMI and peaked within 5 days. Peak TN-C levels were significantly higher in the left ventricular (LV) remodeling group than the non-remodeling group. AMI patients with high TN-C levels were at much higher risk of cardiac death, non fatal AMI, and hospitalization for congestive heart failure. Next, we examined the effects of deletion of TN-C on post-AMI ventricular remodeling using TN-C knockout(KO) mice and compared with those of the wild type(WT). Although no significant difference was detected in survival rate between KO and WT by day 28, The KO mice exerted significantly less LV cavity dilatation, less elevation of endodiastolic left ventricular pressure, and improved fractional shortening and ejection fraction. Histologically, interstitial fibrosis in the residual myocardium is reduced in KO mice. Furthermore, we examined myocardial repair after injury in heart specific TN-C over-expressing mice using a mouse genetic system based on Cre/loxP recombination. With excess expression of TN-C, recruitment of myofibroblasts and myocardial fibrosis was accelerated to compared with that in WT. Although the effects of TN-C on ventricular remodeling are not simple, but rather are bidirectional, it was suggested that excessive and sustained increments of TN-C could inappropriate reconstruction of infarcted ventricular wall and a potential therapeutic target.
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Report
(3 results)
Research Products
(30 results)
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[Journal Article] Higher serum tenascin-C levels reflect the severity of heart failure, left ventricular dysfunction and remodeling in patients with dilated cardiomyopathy.2007
Author(s)
Terasaki F, Okamoto H, Onishi K, Sato A, Shimomura H, Tsukada B, Imanaka-Yoshida K, Hiroe M, Yoshida T, Kitaura Y, Kitabatake A
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Imanaka-Yoshida K, Suzuki K, Yoshida T, Adachi Y, Taguchi O. Deficiency of tenascin C attenuates allergen-induced bronchial asthma in the mouse.2006
Author(s)
Nakahara H, Gabazza EC, Fujimoto H, Nishii Y, D'Alessandro-Gabazza CN, Bruno NE, Takagi T, Hayashi T, Maruyama J, Maruyama K
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Journal Title
Eur J Immunol 36
Pages: 3334-3345
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Method of cell transplantation promoting the organization of intraarterial thrombus.2005
Author(s)
Hirano K, Shimono T, Imanaka-Yoshida K, Miyamoto K, Fujinaga K, Kajimoto M, Miyake Y, Nishikawa M, Yoshida T, Uchida A, Shimpo H, Yada I, Hirata H.
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Description
「研究成果報告書概要(欧文)」より
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