2004 Fiscal Year Final Research Report Summary
Gene expression profiling in hypertrophied heart as the determinant of phenotype of heart failure
| Project/Area Number |
15590742
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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 | Osaka University |
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Principal Investigator |
YAMAMOTO Kazuhiro Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (90303966)
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| Co-Investigator(Kenkyū-buntansha) |
OTSU Kinya Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (20294051)
MIWA Takeshi Osaka University, Genome Information Research Center, Associate Professor, 遺伝情報実験センター, 助教授 (20174229)
MASUYAMA Tohru Hyogo College of Medicine, Professor, 医学部, 教授 (70273670)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Heart Failure / Cardiac Hypertrophy / Remodeling |
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| Research Abstract |
We analyzed gene expression pattern in hypertensive heart using Dahl salt-sensitive rats with diastolic heart failure or systolic heart failure. Expression profiling of mRNA reveals several clusters in approximate 8000 genes using cDNA array method for heart tissue of those different phenotypes of heart failure.
Enhancement of gene expression and activity of matrix metalloproteinases (MMPs ) preceded LV dilatation in a hypertensive heart failure model. Angiotensin converting enzyme (ACE) inhibition suppressed the preceding activation of MMPs and prevented LV remodeling and dysfunction. MMPs are likely to trigger LV remodeling. ACE inhibition directly inhibits MMPs, leading to prevention of heart failure in hypertensive heart. We also analyzed the effects of angiotensin II type 1 receptor Mocker (ARB) and angiotensin converting enzyme inhibitor (ACED on the synthesis and degradation of collagens in a rat model of diastolic heart failure (DHF). Their administration similarly inhibited ventricular fibrosis. The ACEI administration decreased type I collagen mRNA level, but the decrease was less than that induced by the ARB administration. ARB and ACEI inhibited ventricular fibrosis through different mechanisms in DHF. ARB added to ACEI provides more benefits as compared with ACEI alone in DHF when initiated at advanced stage. The additive effects are likely provided through more prominent suppression of ROS generation and inflammatory changes without effects on expression of MCP-1 and TNF-alpha.
N-methylethanolamine (MEA) may exert therapeutic effects on cardiac disorders due to ventricular fibrosis through suppression of phospholipase D (PLD) activity and modulation of fibrosis pathway even without a release from mechanical stress.
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Research Products
(8 results)
