| Project/Area Number |
08407019
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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 | KUMAMOTO UNIVERSITY |
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Principal Investigator |
TASUE Hirofumi Kumamoto University, School of Medicine, Professor, 医学部, 教授 (40174502)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIMURA Michihiro Kumamoto University, School of Medicine, Associate Professor, 医学部・附属病院, 助手 (30264295)
KUGIYAMA Kiyotaka Kumamoto University, School of Medicine, Assistant Professor, 医学部・附属病院, 講師 (00225129)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥19,100,000 (Direct Cost: ¥19,100,000)
Fiscal Year 1998: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1997: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1996: ¥10,800,000 (Direct Cost: ¥10,800,000)
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| Keywords | coronary spasm / angina pectoris / nitric oxide synthase / mutation / cigarette smoking / risk factor / polymorphism / transcrption factor / 一酸化窒素合成酵素 / 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. This conclusion was obtained by intracoronary injection of LNMMA, an inhibitor of nitric oxide synthase (NOS), during cardiac catheterization.
Coronary spasm was mare prevalent in the Japanese than in Caucasian, suggesting that the genetic factor be involved in its pathogenesis. By genetic analysis of the endothelial nitric oxide synthase (eNOS), we have found 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. This finding shows the existence of the genetic factors in coronary spasm. However, it should be empathized that an environmental factors, such as cigarette smoking, is also an important risk factor for coronary spasm.
… More
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. Less
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