| Project/Area Number |
09670732
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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 | Department of Cardiovascular Medicine, Kumamoto University School of Medicine |
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Principal Investigator |
YOSHIMURA Michihiro Dep.of Cardiovasc Med, Kumamoto Univ.Sch.of Med.,, 医学部・附属病院, 助手 (30264295)
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| Co-Investigator(Kenkyū-buntansha) |
YASUE Hirofumi Dep.of Cardiovasc Med, Kumamoto Univ.Sch.of Med., 医学部, 教授 (40174502)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | coronary spasm / angina poctoris / nitric oxide synthase / mutation / transcription factor / myocardial infraction / hypertension / polymorphism / 一酸化窒素合成酸素 / 一酸化窒素 / 一酸化地租合成酵素 / 遺伝子解析 / 冠動脈 |
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| Research Abstract |
In pathophysiological research of coronary spasm, we have recently reported that nitric oxide (NO) activity is deficient in the coronary arteries of patients with coronary spasm. By genetic analysis of the endothelial nitric oxide synthase (eNOS), we have reported a missense Glu298Asp variant in the coding region and 3 linked variants, T-786*C A-922*G and T-1468*A, in the 5'-flanking region of the eNOS gene in patients with coronary spasm. The variants are significantly associated with coronary spasm.
We are now examining whether the eNOS gene variants themselves exert an influence on the synthesis or the activity of eNOS.Our recent in vitro study has reveled that only the T-786*C variant in the 5'-flanking region reduces the promoter activity of the eNOS gene by using luciferase reporter gene assay. Also, our in vivo analysis revealed that the coronary diameter changes evoked by intracoronary injection of acetylcholine or nitroglycerin was greater in patients with the variant type allele than in those with the wild type allele. This accumulated evidence revealed that the T-786*C variant could be thought of as a functional mutation of coronary spasm.
Just recently, we have reported that the eNOS gene variants are associated with other cardiovascular diseases such as myocardial infarction and essential hypertension.
Thus, the series of studies about the eNOS gene variants may bring a new understanding of the pathophysiology of not only coronary spasm but also of other common cardiovascular diseases.
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