| Project/Area Number |
07557345
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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 | 試験 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
YOKOYAMA Mitsuhiro Professor, First department of internal medicine, Kobe university school of medicine, 医学部, 教授 (40135794)
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| Co-Investigator(Kenkyū-buntansha) |
TANIGUCHI Takahiro Assistant Professor, First department of internal medicine, Kobe university scho, 医学部・附属病院, 助手 (20263379)
KAWASHIMA Seinosuke Associate Professor, First department of internal medicine, Kobe university scho, 医学部・附属病院, 講師 (10177678)
KAWAHARA Yasuhiro Associate Professor, First department of internal medicine, Kobe university scho, 医学部, 講師 (80169755)
AKITA Hozuka Associate Professor, First department of internal medicine, Kobe university scho, 医学部, 助教授 (60175792)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1996: ¥3,600,000 (Direct Cost: ¥3,600,000)
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| Keywords | serotonin / coronary spasm / atherosclerosis / vascular smooth muscle / molecular biology / intracellular calcium / acute myocardial infarction / polymorphism / 遺伝子多型性 |
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| Research Abstract |
We have studied the involvement of serotonim (5-HT) and its receptor in the pathogenesis of atherosclerosis and ischemic heart disease. The relults are as follow ;
1.Abnormality in 5-HT-evoked contraction in atherosclerotic vessls
We measured simultaneously isometric tension and intracellular Ca^<2+> in aortae from Watanabe Hereditary Hyperlipidemic (WHHL) rabbits. Although 5-HT-induced contraction in normal aorta was completely blocked by ketanserin, atherosclerotic arora from WHHL rabbits exhibited ketanserin-resistant hypercontraction to 5-HT,suggesting the involvement of 5-HT1-like receprors. The augmented Ca^<2+> mobilization but no the altered Ca^<2+> sensitivity of contractile component was accompanied by this augmented contratile response to 5-HT.
2.Molecular analysis of 5-HT receptors in human coronary artery (HCA)
RNase protection assay was performed using total RNA extracted from post-mortem human coronary arteries to clarify 5-HT receptor subtypes in HCA.It revealed the predominant expression of 5-HT1Dbeta and 5-HT2A receptors mRNA in HCA.5-HT1Dbeta receptor mRNA was upregulated in HCA with atherosclerosis. These findings suggest that contraction mediated through 5-HT1Dbeta receptor might play an important role in the augmented contractile respomse to 5-HT in atherosclerotic HCA.
3.Acute myocardial infarction (AMI) and polymorphism of 5-HT2A receptor gene
We examined the association between AMI and 5-HT2A receptor T^<102> C polymorphism. Frequency of TT and TC genotype was significantly increased in patients with AMI.Our findings indicate that polymorphism of 5-HT2A receptor gene may be an independent risk factor of AMI.
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