| Project/Area Number |
05454325
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
YAMAMURA Taku National Cardiovascular Center Research Institute, Department of Etiology and Pahtophysiology, Head of Laboratory, 病因部, 室長 (20132938)
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| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Takao National Cardiovascular Center Research Institute, Department of Etiology and Pa, 病因部, レジデント研究員
MIYAKE Yasuko National Cardiovascular Center Research Institute, Department of Etiology and Pa, 病因部, 室長 (00132936)
豊田 康嗣 国立循環器病センター研究所, 病因部, レジデント
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1993: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Keywords | Apolipoprotein / LDL receptor / Hyperlipoproteinemia / Atherosclerosis / Lipoprotein |
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| Research Abstract |
1.Applipoprotein E Mutants and Lipoprotein Metabolism
Apo E mutants, E5 and E7, were produced by Chinese hamster ovary cells by means of gene technology. They were highly consistent with those obtained from plasma. We investigated the distribution of apo E5 and apo E7 among the plasma lipoproteins, and the heparin-binding activities of these mutants. Both apo E5 and apo E7 were more prominent in the VLDL fraction than in the HDL fraction. Apo E7 displayd a stronger interaction with heparin than apo E3. This may be one of the mechanisms producing atherosclerotic disease in patients with the apo E7 mutant.
2.Abnormalities of Apolipoprotein B and Low Density Lipoprotein
We analyzed the binding affinity of LDL from patients with hyperlipoproteinemia to the LDL receptor. Familial defective apo B-100 (Arg_<3500>*Gin) was not found in the present study. However, LDL from patients with hypertriglyceridemia showed a low affinity to the LDL receptor. The LDL was rich in protein, poor in lipids, and
… More
smaller than LDL from controls. These structural and functional abnormalities were reversed by drug therapy, emphasizing the importance of treating hypertriglyceridemia for the prevention of atherosclerosis.
3.Lipoprotein (a) as a Risk Factor for Atherosclerosis
We investigated the association between Lipoprotein (a) [Lp (a) ] and atherosclerosis. Even in normocholesterolemic subjects, elevated serum Lp (a) was linked to atherosclerosis and influenced its severity. While it is reported that there is an inverse relationship between the size of apo (a) and plasma Lp (a) concentrations, we found wide variations of Lp (a) values in each apo (a) isoform. Our results suggested that apo E phenotype may be one of other factors influencing the plasma Lp (a) concentration.
4.Apo A-1 and Apo A-IV in animal models for Atherosclerosis
We developed a enzyme immunoassay for rabbit apo A-I and apo A-IV.Watanabe heritable hyperlipidemic rabbit (WHHL-R) caused reduced levels of apo A-I and apo A-IV.The distribution of apo A-IV in WHHL-R was shifted towards the lipoprotein-free pool. These results show an impaired reverse transport of cholesterol in WHHL-R.We investigated the effects of reconstituted high-density lipoprotein (r-HDL) on atherosclerosis. Injection of r-HDL caused slight inhibition of atherogenesis, but neither change was statistically significant, indicating that the physiological properties of artficial and nativelipoproteins may differ. Less
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