| 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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| 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
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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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