2005 Fiscal Year Final Research Report Summary
Establishment of a new treatment target for ischemia-related heart failure and arrhythmia-related sudden death
| Project/Area Number |
16590684
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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 |
OHISHI Mitsuru Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (50335345)
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| Co-Investigator(Kenkyū-buntansha) |
OGIHARA Toshio Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (60107042)
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| Project Period (FY) |
2004 – 2005
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| Keywords | ACE2 / knockout mice / heart failure / survival ratio / AT1 receptor / MAP kinase / local RA system / heart failure death |
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| Research Abstract |
Angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase that cleaves angiotensin II to angiotensin 1-7. Recently, it was reported that mice lacking ACE2 (ACE2^<-/y> mice) exhibited reduced cardiac contractility. Because mechanical pressure overload activates the cardiac renin-angiotensin system, we used ACE2^<-/y> mice to analyze the role of ACE2 in the response to pressure overload. Twelve-week-old ACE2^<-/y> mice and wild-type (WT) mice received transverse aortic constriction (TAC) or sham operation. Sham-operated ACE2^<-/y> mice exhibited normal cardiac function and had morphologically normal hearts. In response to TAC, ACE2^<-/y>mice developed cardiac hypertrophy and dilatation. Furthermore, their hearts displayed decreased cardiac contractility and increased fetal cardiac gene induction, compared with WT mice. In response to chronic pressure overload, ACE2^<-/y> mice developed pulmonary congestion and increased incidence of cardiac death compared with WT mice. On a biochemical level, cardiac angiotensin II concentration and activity of mitogen-activated protein (MAP) kinases were markedly increased in ACE2^<-/y> mice in response to TAC. Administration of candesartan, an AT_1 subtype angiotensin receptor blocker, attenuated the hypertrophic response and suppressed the activation of MAP kinases in ACE2^<-/y> mice. Activation of MAP kinases in response to angiotensin II was greater in cardiomyocytes isolated from ACE2^<-/y> mice than in those isolated from WT mice. ACE2 plays an important role in dampening the hypertrophic response to pressure overload mediated by angiotensin II. Disruption of this regulatory function may accelerate cardiac hypertrophy and shorten the transition period from compensated hypertrophy to cardiac failure.
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Research Products
(24 results)
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[Journal Article] Deletion of ACE2 accelerates pressure-overload-induced cardiac dysfunction by increasing local angiotensin II2006
Author(s)
Yamamoto K, Ohishi M, Katsuya T, Ito N, Ikushima M, Kaibe M, Tatara Y, Shiota A, Sugano S, Takeda S, Rakugi H, Ogihara T.
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Journal Title
Hypertension 47
Pages: 718-726
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Association of Hypoadiponectinemia With Smoking Habit in Men.2005
Author(s)
Iwashima Y, Katusya T, Ishikawa K, Kida I, Ohishi M, Horio T, Ouchi N, Ohashi K, Kihara S, Funahashi T, Rakugi H, Ogihara T.
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Journal Title
Hypertension 45
Pages: 1094-1100
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Relationship of bradykinin B2 receptor gene polymorphism with essential hypertension and left ventricular hypertrophy.2004
Author(s)
Fu Y, Katsuya T, Matsuo A, Yamamoto K, Akasaka H, Takami Y, Iwashima Y, Sugimoto K, Ishikawa K, Ohishi M, Rakugi H, Ogihara T.
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Journal Title
Hypertens Res 27
Pages: 933-938
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hypoadiponectinemia is an Independent Risk Factor for Hypertension2004
Author(s)
Iwashima Y, Katsuya T, Ishikawa K, Ouchi N, Ohishi M, Sugimoto K, Fu Y, Motone M, Yamamoto K, Matsuo A, Ohashi K, Kihara S, Funahashi T, Rakugi H, Matsuzawa Y, Ogihara T.
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Journal Title
Hypertension 43
Pages: 1318-1323
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Association between hepatocyte growth factor gene polymorphism and essential hypertension.2004
Author(s)
Motone M, Katsuya T, Ishikawa K, Iwashima Y, Sugimoto K, Yamamoto K, Fu Y, Matsuo A, Ohishi M, Rakugi H, Ogihara T.
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Journal Title
Hypertens Res 27
Pages: 247-252
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Adiponectin 1164T mutation is associated with the metabolic syndrome and coronary artery disease.2004
Author(s)
Ohashi K, Ouchi N, Kihara S, Funahashi T, Nakamura T, Sumitsuji S, Kawamoto T, Matsumoto S, Nagaretani H, Kumada M, Okamoto Y, Nishizawa H, Kishida K, Maeda N, Hiraoka H, Iwashima Y, Ishikawa K, Ohishi M, Katsuya T, Rakugi H, Ogihara T, Matsuzawa Y.
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Journal Title
J Am Coll Cardiol 43
Pages: 1198-1200
Description
「研究成果報告書概要(欧文)」より
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