1992 Fiscal Year Final Research Report Summary
Platelet and atherosclerosis, with special reference to interaction between platelets and lipoproteins.
| Project/Area Number |
02454515
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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 |
Hematology
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| Research Institution | Yamanashi Medical College |
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Principal Investigator |
KUME Shoji Yamanashi Medical College, Department of Laboratory Medicine, Professor., 医学部, 教授 (50010492)
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| Co-Investigator(Kenkyū-buntansha) |
OZAKI Yukio Yamanashi Medical College, Department of Laboratory Medicine, Associate Professo, 医学部, 助教授 (30134539)
TERAMOTO Tamio Tokyo University School of Medicine, 1 st Department of Internal Medicine, Assis, 医学部, 助手 (20133077)
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| Project Period (FY) |
1990 – 1992
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| Keywords | LDL / HDL / platelet / hyperlipidemia / apoE / cholesterol / liposome / リポソーム |
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| Research Abstract |
1) Effect of low-density lipoprotein (LDL) on platelet function. LDL(d=1.019-1.050) binds to human platelets with the dissociation constant (Kd) of 58nM and 1750 binding sites per platelet. LDL at a concentration under 1mg/ml induces a transient increase in intracellular Ca^<2+> concentration and a shape change of human platelets, but does not release granules, induce thromboxane B_2 formation or protein phosphorylation. LDL at a concentration of 100mug/ml which is near Kd of LDL-binding had a maximal stimulatory effect on agonist-induced platelet aggregation. LDL binding on platelets is Ca^<2+>-independent and displaced by high density lipoprotein (HDL). These results suggest that LDL enhances agonist-induced platelet activation via platelet-type LDL receptors differing from classical LDL receptors.
2) Effect of high-density lipoprotein (HDL) on platelet function Apolipoprotein E -(ApoE-) rich HDL of normal subjects and hyperalphalipoproteinemic patients, showed marked inhibitory effects on platelet aggregation and ATP release as compared with apoE-poor HDL, suggesting that apoE has inhibitory effects on platelet function. Dimyristoyl phosphatidylcholine liposome with apoE (apoE・DMPC) also inhibited platelet aggregation, and incubation of washed platelets with apoE・DMPC resulted in the release of cholesterol into the supernatant. These results suggest that apoE plays a major role in the inhibitory effect of apoE-rich HDL on platelet function, presumably due to the release of cholesterol from the plasma membrane.
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