1995 Fiscal Year Final Research Report Summary
Role of Cardiac Specific Renin-Angiotensin Sytem in Cardiac Hypertrophy-Studies on Transgenic Mouse
| Project/Area Number |
06404033
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Hokkaido University |
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Principal Investigator |
KITABATAKE Akira Hokkaido University Medicine, Professor, 医学部, 教授 (00124769)
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| Co-Investigator(Kenkyū-buntansha) |
OIKAWA Tuneyuki Sasaki Institute, Director, 細胞遺伝部, 部長 (80150241)
OKAMOTO Hiroshi Hokkaido University Hospital, Assistant Professor, 医学部・附属病院, 助手 (50260394)
KAWAGUCHI Hideaki Hokkaido University Medicine, Professor, 医学部, 教授 (70161297)
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| Project Period (FY) |
1994 – 1995
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| Keywords | cardiac hypertrophy / renin-angiotensin system / transgenic mouse / heart failure / gene polymorphism / cardiomyopathic hamster / angiotensinogen / angiotensin-converting enzyme |
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| Research Abstract |
The aim of this research project was to establish the transgenic mouse, which would be made by transfer renin-angiotensin system genes with cardiac specific promotor to mouse oocytes to clarify the tissue-apecific role of genes of renin-angiotensin system in hte mechanism of cardiac hypertrophy. We have demonstrated that hypertrophic cardiomyopathy (HCM), especially in sporadic cases, is partially determined by genetic disposition and the molecular variant of angiotensin-converting enzyme D allele and angiotensinogen T235 seems to be a predisposing factor for cardiac hypertrophy. We have reported that in the experimental models of cardiac hypertrophy, gene expressions for renin, angiotensinogen, and angiotensin-converting enzyme were enhanced and signals leading to hypertrophy were processing through angiotensin type1 receptor and Gq coupling inositol phosphatide metabolism. We also obtained cardiac-specific promotor region of myosin to express the transfected gene within the heart. We have developed an adenovirus mediated gene transfer system, in which angiotensin-converting enzyme gene can easily transfected in vivo. Although ther remain several steps to be overcome before making transgenic animal models of the renin-angiotensin system, these sophisticated studies provide original and important findings in the field of molecular cardiology.
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[Publications] Ishanov A,Okamoto H,Yoneya K,Watanabe M,Nakagawa I,Onozuka H,Mikami T,Kawaguchi H,Hata A,Kondo K,Kitabatake A.: "Angiotensinogen Gene polymorphism in Japanese patients with Hypertrophic cardiomyopathy." Am Heart J Machida M. 133. 184-189 (1997)
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