| Project/Area Number |
10557048
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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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) |
SAITO Takeshi Tokai Univ, School of Medicine, Assistant Researcher, 医学部, 助手 (30266465)
YUKAWA Nobuhiro Tokai Univ.School of Med.Associate Professor, 医学部, 助教授 (30240154)
OSAWA Motoki Yamagata University, School of Medicine, Professor, 医学部, 教授 (90213686)
TANAKA Akira Tokyo Medical and Dental University, School of Medicine, Assistant professor, 医学部, 講師 (70171733)
OKAZAKI Mituyo Tokyo Medical and Dental University School of Medicine, Professor, 教養部, 教授 (20013998)
NAKAJIMA Katsuyuki Otsuka America Pharmaceutical Inc.
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2000: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1999: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1998: ¥7,000,000 (Direct Cost: ¥7,000,000)
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| Keywords | Sudden cardiac death / Pokkuri disease / Remnant-like particles (RLP) / Remnant hyperlipoproteinemia / Platelet aggregation / Vasospasm / ApoB-48 / Angiography / アポB48 / 冠動脈硬化度 / 危険因子 / 心臓性突然死(Sudden Cardiac Death;SCD) / RLP(remnant-like particles) / RLP-C / RLP-TG / アポB100 / HPLC法 / 攣縮誘発試験 / remnant-like Particles(RLP) / 冠動脈硬化進展度 / 血小板凝集能 / 血管攣縮(冠動脈攣縮) / レムナント分画の脂肪酸分析 / アポ蛋白遺伝子塩基置換 / 死後変化 |
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| Research Abstract |
Most cases of sudden cardiac death (SCD) are associated with severe atherosclerosis. However, approximately 10% of SCD cases occur with minimal atherosclerosis, namely "Pokkuri disease". In order to understand these latter deaths, we investigated the relationship of SCD with postprandial remnant hyperlipoproteinemia using the remnant-like particles (RLP) assay. In order to analyze postmortem plasma samples, we modified the assay to measure RLP-C (cholesterol) and RLP-TG (triglyceride). RLP-C concentrations were highly correlated with the progression of atherosclerosis, while RLP-TG was associated with an enhancement of platelet aggregation and inhibition of vasorelaxation, may be associated with "Pokkuri disease".
The genetic disorder underlying SCD was also studied using the lipoprotein lipase and apo E.A point mutation frequency of lipoprotein lipase DNA (Asn291Ser, Ser447Stop) and a mutation of apo E (Cys112Arg ; E4, Arg158Cys ; E2) were related to increased levels of remnant lipopro
… More
teins. These results indicated that SCD cases showed a higher frequency of mutations.
The association between increased lipoprotein remnants and SCD, including genetic and environmental factors, has been studied in order to clarify the causes of acute coronary artery events and eventually to prevent sudden cardiac death. We have analyzed plasma lipids and lipoproteins in patients with acute coronary artery disease diagnosed by angiography. Apo B-48 concentrations were highly correlated with the severity of atherosclerosis, more so than either RLP-C or RLP-TG.Most of the patients were taking medications (mainly lipid lowering drug) ; nevertheless levels of apo B-48 were shown to be significantly high and not well controlled by conventional lipid lowering drugs.
Recently, Bradley and Gianturco discovered an apo B-48 receptor, which binds remnant lipoproteins (especially the apo B-48 containing chylomicron remnants). We plan to investigate the association between remnant metabolism and SCD with relation to the apo B-48 receptor gene mutation. Less
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