1997 Fiscal Year Final Research Report Summary
Gene analysis of hypertension and development of new therapy
| Project/Area Number |
07407021
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 |
OGIHARA Toshio Osaka University Medical School, Professor, 医学部, 教授 (60107042)
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| Co-Investigator(Kenkyū-buntansha) |
MORISHITA Ryuichi Osaka University Medical School, Assistant Professor, 医学部, 助手 (40291439)
MORIGUCHI Atsushi Osaka University Medical School, Assistant Professor, 医学部, 助手 (10273666)
RAKUGI Hiromi Osaka University Medical School, Assistant Professor, 医学部, 助手 (20252679)
HIGAKI Jitsuo Osaka University Medical School, Associate Professor, 医学部, 助教授 (70189744)
MIKI Tetsuro Osaka University Medical School, Associate Professor, 医学部, 助教授 (00174003)
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| Project Period (FY) |
1995 – 1997
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| Keywords | gene / hypertension / gene analysis / gene therapy / vascular remodeling / NFkB |
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| Research Abstract |
1. Gene analysis of hypertension
We examined the association between variants in the core promotor element 1 (AGCE1) of the human angiotensinogen gene, which acts as a critical regulator of angiotensinogen transcription. The results obtained was that C-18T polymorphism in AGCE1 is a genetic risk factor for essential hypertension in Japanese. These results suggest that dysfunction of promortor element of angiotensinogen gene may be related to the genetic pathogenesis of hypertension.
2. Gene therapy of cardiovascular diseases
The transcriptional factor NFkB plays a pivotal role in the coordinated transactivation of cytokine and adhesion molecule genes that might be involved in myocardial damage after ischemia and reperfusion. Then we transfected synthetic double-stranded DNA with high affinity for NFkB before or after the cardiac ischemia in rats. We showed that the first successful in vivo tranfer of NFkB decoy oligodeoxynucleotides to reduce the extent of myocardial infraction following reperfusion, providing a new therapeutic strategy for myocardial infarction.
3.Pathogenesis of cascular remodeling
We conducted histopathological study on the atheroscleosis in human coronary arteries. In the culpit region of coronary atherosclerosis, we showed over-expression of angiotensinogen and angiotensin converting-enzyme. We showed the direct evidence of the role of the tissue-renin angiotensin system in the coronary-aterosclerosis.
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