| Project/Area Number |
13557066
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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 | Kobe University |
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Principal Investigator |
YOKOYAMA Mitsuhiro Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Professor, 大学院・医学系研究科, 教授 (40135794)
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| Co-Investigator(Kenkyū-buntansha) |
HIRATA Ken-ichi Kobe University, Kobe University Hospital, Lecturer, 医学部附属病院, 講師 (20283880)
KAWASHIMA Seinosuke Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10177678)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2002: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Keywords | lipase / lipoprotein / atherosclerosis / endothelial cell / smooth muscle cell / macrophage / coronary arteries / molecular cloning / 高脂血症 / サイトカイン / 炎症 / 高比重リポ蛋白質 / ELISA / HDL |
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| Research Abstract |
We and another group have cloned independently a new member of the LPL gene family, endothelial cell-derived lipase (EDL) that is produced by vascular endothelial cells. We have established ELISA system to measure the plasma EDL level in humans and are measuring the plasma EDL levels in normal volunteers and patients with ischemic heart diseases. Conversely, EDL knockout mice showed a marked elevation in HDL cholesterol levels. These data suggest that EDL may play a physiologic role in HDL metabolism. Immunohistochemical analysis revealed that EDL was expressed in endothelial cells and medial smooth muscle cells in non-atherosclerotic coronary arteries. In addition, EDL was detected in infiltrating cells within atheromatous plaques as well as endothelial and smooth muscle cells. To investigate local control of lipase activity and lipid metabolism in the blood vessel wall, we have examined the regulation of EDL expression in HCAECs and HCAECs. EDL mRNA levels were unregulated in both cell types by inflammatory cytokines implicated in vascular disease etiology, including TNF-α and IL-1β. Moreover, both fluid shear stress and cyclic stretch were found to increase the EDL mRNA levels in these cultured cells. To gain better understanding of the function of EDL in vivo, we have generated mice that lack EDL gene. EDL-/- mice are viable and fertile and do not exhibit any overt defects or body weight differences. Fasting plasma HDL cholesterol was increased in heterozygous mutant (EDL+/-) mice, compared with wild type (WT) mice. In contrast, there was no significant difference in triglyceride levels among these genotypes. In conclusion, EDL is an important regulator of HDL metabolism in vivo and likely mediates endothelium-lipoprotein interactions, and EDL in vascular cells may be involved in modulating vessel wall lipid metabolism and may play a role in vascular diseases such as atherosclerosis.
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