2005 Fiscal Year Final Research Report Summary
Molecular mechanisms and novel therapeutic approaches for cardiovascular calcification
| Project/Area Number |
15390239
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | The University of Tokyo |
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Principal Investigator |
OUCHI Yasuyoshi The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (80168864)
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| Co-Investigator(Kenkyū-buntansha) |
ETO Masato The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (80282630)
IIJOMA Katsuya The University of Tokyo, Faculty of Medicine, Project Lecturer, 医学部附属病院, 特任講師 (00334384)
OHIKE Yumiko The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (20359615)
KOJIMA Taro The University of Tokyo, Faculty of Medicine, Medical Staff, 医学部附属病院, 医員
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| Project Period (FY) |
2003 – 2005
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| Keywords | vascular calcification / human aortic smooth muscle cells / Na-dependent Pi cotransporter / apoptosis / Gas6 |
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| Research Abstract |
In this research project, we have gained several findings as described below.
(1) We have established in vitro model of vascular calcification using human aortic smooth muscle cells (HASMC). In this model, we have observed that phosphate-induced SMC calcification involves osteoblast-like transformation via Na-dependent Pi cotransporter activation. Furthermore, we have got the results showing that phosphate induced SMC calcification as well as apoptosis in a concentration-dependent manner and the inhibition of apoptosis by the caspase inhibitor prevented SMC calcification, suggesting the essential role of SMC apoptosis in calcification. We have also identified the downregulation of Gas6 and its receptor Axl as a cause of phosphate-induced SMC apoptosis and calcification.
(2) We examined the effects of statins on SMC calcification. Statins prevented both SMC apoptosis as well as calcification. In addition, the inhibitory effects of statins were mainly mediated by the restoration of the downregulation of Gas6 and Axl induced by phosphate.
(3) We have also established in vivo rat model of vascular calcification and confirmed the beneficial effects of statins, observed in in vitro model. Statins markedly suppressed aortic calcification in rat model of renal failure induced by adenine supplementation.
(4) To identify the correlates with vascular calcification in patients, we evaluated the length of abdominal aortas in XP of 42 elderly patients and investigated the correlations with several variables. As a result, we found the positive correlation between length of aortic calcification and pulse pressure (r=0.54,p<0.01), suggesting aortic calcification as a structural substrate of aortic stiffness.
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[Journal Article] Sirt1 inhibitor, Sirtinol, induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells. Oncogene.2006
Author(s)
Ota H, Tokunaga E, Chang K, Hikasa M, Iijima K, Eto M, Kozai K, Akishita M, Ouchi Y, Kaneki M.
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Journal Title
Oncogene. 25(2)
Pages: 176-185
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Impact of blood pressure variability on cardiovascular events in elderly patients with hypertension.2005
Author(s)
Eto M, Toba K, Akishita M, Kozaki K, Watanabe T, Kim S, Hashimoto M, Ako J, Iijima K, Sudoh N, Yoshizumi M, Ouchi Y.
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Journal Title
Hypertens Res. 28(1)
Pages: 1-7
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Amelioration of vascular endothelial dysfunction in obstructive sleep apnea syndrome by nasal continuous positive airway pressure--possible involvement of nitric oxide and asymmetric NG, NG-dimethylarginine.2005
Author(s)
Ohike Y, Kozaki K, Iijima K, Eto M, Kojima T, Ohga E, Santa T, Imai K, Hashimoto M, Yoshizumi M, Ouchi Y.
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Journal Title
Circ J. 69(2)
Pages: 221-226
Description
「研究成果報告書概要(欧文)」より
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