| Project/Area Number |
14570396
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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 |
Legal medicine
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| Research Institution | Tokai University |
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Principal Investigator |
TAKEICHI Sanae Tokai University, School of Medicine, Professor, 医学部, 教授 (20035497)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Katuyuki Japan Immunoresearch Laboratory Co.,Ltd, Director, 開発部長(研究職)
GOTOH Shinya Tokai University, School of Medicine, Associate Professor, 医学部, 助教授 (50225653)
SATOH Fumiko Tokai University, School of Medicine, Assistant Researcher, 医学部, 助手 (70328128)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Pokkuri disease / Remnant lipoproteins (RLP) / Sudden Coronary Death / Coronary Spasm / NO / Rho-kinase / Postmortem stability / Pregnancy / レムナント・リポ蛋白 / 妊婦 / remnant lipoproteins / RLP-TG / Rho / 心臓性突然死 / Hydroxyfasudil |
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| Research Abstract |
Our present research has revealed the following new facts related to coronary spasm, which we believe is the direct cause of Pokkkuri disease.
1.We have clarified the role of endothelium-derived nitric oxide (NO)on coronary artery spasm by RLP isolated from the sudden cardiac death(SCD) cases. NO production in bovine endothelial cells was inhibited by RLP in a dose dependent manner. The amount of NO synthase (eNOS) was not dicreased, but the enzyme activity was suppressed by RLP.
2.Recently the increased activity of Rho-kinase in vascular smooth muscle cells has been known to play a major role in the pathogenesis of coronary artery spasm. Our in vivo study demonstrated that long -term treatment with RLP, but not with nascent VLDL from patients with SOD markedly enhanced coronary vasospastic activity in porcine coronary arteries. We then demonstrated in cultured human coronary vascular smooth muscle cells that the treatment of RLP significantly enhanced the expression and activation of Rho-kinase. Rho-kinase inhibitor, hydoxyfasdil completely inhibited this effect.
3.Validity of postmortem plasma remnant lipoprotein assay was studied in order to confirm the analysis of postmortem plasma. The postmortem alteration of lipids and lipoproteins were observed by the following methods ; Dry Chem TG and Determiner L-TG assay, HPLC profile analysis, electrophoresis, electron microscopy and rabbit ante-and postmortem plasma. We found that plasma lipid and lipoprotein levels determined in postmortem state did not differ significantly from antemortem levels
In addition to the above results
4.We have found that hypertriglyceridemia in pregnancy did not contribute to the elevation of RLP-C/VLDL-C ratio and RLP-TG/VLDL-TG ratio. These ratios were significantly low in pregnancy compared with diabetic patients and other cardiovascular disease. These results strongly point to the fact that Pokkuri disease is more common in males than in females.
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