2005 Fiscal Year Final Research Report Summary
Analysis of defense mechanism of heme oxygenase against cardiovascular disorders and its clinical application
| Project/Area Number |
16590703
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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 | Fukushima Medical University |
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Principal Investigator |
ISHIKAWA Kazunobu Fukushima Medical University, The first internal medicine, Lecturer, 医学部, 講師 (80222959)
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| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Yukio Fukushima Medical University, The first internal medicine, Professor, 医学部, 教授 (90004712)
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| Project Period (FY) |
2004 – 2005
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| Keywords | heme oxygenase / bilirubin / carbon monoxide / endothelium / macrophage / cardiomyopathy / oxidative stress / knockout mouse |
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| Research Abstract |
We have analyzed the anti-atherogenic mechanism of heme oxygenase-1 (HO-1) in vascular endothelium (Arterioscler Thromb Vasc Biol.2005,25:155). Bilirubin, one of the reaction products of HO-1, prevented pro-inflammatory endothelial activation and dysfunction after the exposures to oxidized LDL and TNF-α. Bilirubin suppressed the increases of cytokines and growth factors such as VCAM-1, MCP-1 and MCSF that involve the progression of atherosclerosis. Bilirubin also preserved the expression of eNOS and acetylcholine-dependent vascular relaxation response. These effects were mediated by predominantly by bilirubin whereas carbon monoxide (CO), another HO product, did not show apparent effects. Effects of HO-2 on atherogenesis were examined by HO-2/LDL-receptor double knockout mice. In addition, alteration of ventilatory response against hypoxia in HO-2 knockout mice were analyzed(Biochem Biophys Res Commun 2004,320:514). We have also reported HO-1 was over expressed in the heart, where increased reactive oxygen species were generated, of the patient with mitochondrial cardiomyopathy (Circ J.2005,69:617-620). Different protective mechanisms of HO-1 in vascular endothelium and macrophages were presented in the plenary session of the 69^<th> Japanese Circulation Society Meeting.
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[Journal Article] Hypoxemia and attenuated hypoxic ventilatory responses in mice lacking heme oxygenase-2 : evidence for a novel role of heme oxygenase-2 as an oxygen sensor.2006
Author(s)
Zhang Y, Furuyama K, Adachi T, Ishikawa K, Matsumoto H, Masuda T, Ogawa K, Takeda K, Yoshizawa M, Ogawa H, Maruyama Y, Hida W, Shibahara S.
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Journal Title
Adv Exp Med Biol 580
Pages: 161-166
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hypoxemia and blunted hypoxic ventilatory responses in mice lacking heme oxygenase-2.2004
Author(s)
Adachi T, Ishikawa K, Hida W, Matsumoto H, Masuda T, Date F, Ogawa K, Takeda K, Furuyama K, Zhang Y, Kitamuro T, Ogawa H, Maruyama Y, Shibahara S.
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Journal Title
Biochem Biophys Res Commun 320
Pages: 514-522
Description
「研究成果報告書概要(欧文)」より
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