| Project/Area Number |
18590583
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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 |
Hygiene
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
NIWA Yasuharu National Cardiovascular Center Research Institute, Research institute, Laboratory chief (40284286)
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| Co-Investigator(Kenkyū-buntansha) |
IWAI Naoharu Research institute, 疫学部, Head of department (30242978)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,810,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Nano materials / Genetics / Animal / Circulation / Hypertension / Cancer |
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| Research Abstract |
Background : Nanomatenals have numerous potential benefits for society, but the potential hazards of nanomatenals on human health are poorly understood. Nanomaterials are known to pass into the circulatory system in humans, causing vascular injuries that may play a role in the development of atherosclerosis. This study aimed to determine the effects of chronic exposure to nanomaterials on macrophage phenotype and platelet aggregation.
Methods and Results : Cultured macrophages(RAW264.7) were treated with carbon black(CB) and water-soluble fullerene(C_<60>(OH)_<24>) from 7 to 50 d. Individually, CB had no significant effects on RAW264.7 cell growth while C_<60>(OH)_<24> alone or CB, C_<60>(OH)_<24> together with oxidized-LDL(Ox-LDL) (100 □g/ml) induced cytotoxic morphological changes such as Ox-LDL uptake-induced foam cell-like formation and decreased cell growth, in a dose-dependent manner. C_<60>(OH)_<24> induced LOX-1 protein expression, pro-MMP-9 protein secretion, and Tissue factor
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mRNA expression in lipid-laden macrophages. Although CB or C_<60>(OH)_<24> alone did not induce platelet aggregation, C_<60>(OH)_<24> facilitated ADP-induced platelet aggregation. Furthermore, C_<60>(OH)_<24> acted as a competitive inhibitor of ADP receptor antagonists in ADP-mediated platelet aggregation.
Conclusions : The present study confirmed novel effects of nanomaterials in macrophages and platelets. These suggest that exposure to nanomaterials may be a risk for atherothrombotic diseases.
Background : Associations between exposures to particulate matters and susceptibility to cardiovascular events have been reported. Although the underlying mechanisms are not fully understood, this association seems to be exaggerated especially in the presence of atherothrombotic risk factors. The present study was undertaken to test the hypothesis that long-term exposure to a high dose of nano-sized carbon black(CB) exacerbates atherosclerotic lesions in low density lipoprotein receptor knockout(LDLR/KO) mice.
Methods and Results : LDLR/KO mice were subjected to a 10-week intra-tracheal dispersion of CB(1mg/wk) or air under a 0% or 0.51% cholesterol diet. Development of aortic lipid-rich lesions was detected in mice under a 0.51% cholesterol diet with or without CB dispersion but not in mice fed a 0% cholesterol diet with or without CB. Quantification of the area stained with oil red O revealed the highest percentage in CB-treated mice on a 0.51% cholesterol diet among the four groups. One-way ANOVA indicated CB-treated mice with 0.51% cholesterol diet had a significantly higher percentage of positive staining than vehicle-treated mice with 0.51% cholesterol diet(p<0.05).
Conclusions : In LDLR-deficient mice under a high cholesterol diet, exposure to CB resulted in acceleration of development of atherosclerosis.
Objectives : Nanomaterials have numerous potential benefits for society, but the effects of nanomatenals on human health are poorly understood Less
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