2000 Fiscal Year Final Research Report Summary
Establishment of A New Strategy for the Treatment of Atherosclerosis by Activating Reverse Cholesterol Transport
| Project/Area Number |
11557054
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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 |
Circulatory organs internal medicine
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| Research Institution | Osaka University Graduate School of Medicine |
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Principal Investigator |
SAKAI Naohiko Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (80294073)
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| Co-Investigator(Kenkyū-buntansha) |
HIRANO Kenichi Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手
FUNAHASHI Tohru Osaka University Graduate School of Medicine, Lecrurer, 医学系研究科, 講師 (60243234)
YAMSHITA Shizuya Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (60243242)
ARAGANE Katsumi Fujirebio Inc., Researcher, 中央研究所・医薬第8研究室, 研究員
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| Project Period (FY) |
1999 – 2000
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| Keywords | Cdc42Hs / high density lipoprotein (HDL) / reverse cholesterol transport / Tangier disease / efflux / atherosclerosis / lipid transport / cDNA subtraction |
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| Research Abstract |
Cholesterol efflux (CE) is the initial and important step of reverse cholesterol transport, a major protective system against atherosclerosis. Tangier disease (TD) is a familial HDL deficiency the primary defect of which is characterized by the abnormality in CE by HDL from peripheral cells. cDNA subtraction revealed that the expression of a member of the Rho GTPase family, Cdc42Hs, was markedly decreased in both passaged fibroblasts and macrophages from patients with TD.We demonstrated that MDCK cells expressing the dominant negative form of Cdc42Hs had reduced CE, whereas those expressiong the dominant active form had increased CE, suggesting that Cdc42Hs is one of the intracellular molecules involved in CE.In addition, the FRAP (fluorescence recovery after photobleaching) revealed that the intracellular lipid transport is retarded in TD fibroblasts which is probably associated with the impaired CE.The fibroblasts from TD patients infected with recombinant adenovirus expressing dominant form of Cdc42Hs recovered the normal CE and intracellular lipid transport. Thus, the decreased expression of Cdc42Hs is demonstrated to be related to the pathophysiology of TD.The finding of the Cdc42Hs as an intracellular molecule involved in CE possibly contributes the establishment of a new strategy for the treatment of atherosclerosis by activating CE by HDL from peripheral cells, especially mcrophages.
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