| Project/Area Number |
13670711
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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 |
Circulatory organs internal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
ISHIKAWA Yuichi Kobe University Graduate School of Medicine, Division of Health Sciences, Professor, 医学部, 教授 (90159707)
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| Co-Investigator(Kenkyū-buntansha) |
KAWASHIMA Seinosuke Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Intemal Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10177678)
TANIGUCHI Takahiro Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Intemal Medicine, Assistant Professor, 大学院・医学系研究科, 講師 (20263379)
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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 |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | chylomicron remnants / endothelial cells / vascular smooth muscle cell / apoptosis / monocyte chemoattractant protein 1 / 血管内非細胞 / 血管平滑筋細胞 / アポートシス / 細胞内シグナル伝達 |
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| Research Abstract |
All forms of percutaneous coronary intervention confer injury on the vessel. The arterial response to that injury is the basis for long-term outcome. Neointima forms in response to thrombus, inflammation, intimal and medial dissections, and elastic recoil of the arterial wall when augioplasry was performed. Chylomicron remnants, major lipoproteins at postprandial hyperlipidemia, is considered to be proatherogenic lipoproteins. However, the mechanisms by which chylomicron remnants enhance atherosclerosis have not been fully understood. Here, we examined the effect of chylomicron remnants on endothelial cells and smooth muscle cells. We prepared chylomicrons from the lymph of the rats which were fed with egg solution and obtained chylomicron remnants from the plasma of functionally hepatectomized rats injected with chylomicrons. First, we examined the effect of chylomicron remnants on human umbilical vein endomelial cells (HUVECs). Chylomicron remnants activated caspase-3 activity and in
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duced apoptosis of HUVECs in a dose dependent manner. Next, we investigated the effect of chylomicron remnants on monocyte chemoattractant protein-1 (MCP-1) expression in cultured vascular smooth muscle cells (VSMCs). MCP-1 is a chemokine, which stimulates migration of monocytes and plays a critical role in the development of atherosclerosis. Treatment of VSMC with chylomicron remnants significantly increased the expression of MCP-1 mRNA and protein in a time-and dose-dependent manner. Furthermore, chylomicron remnants activated p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK1/2). Pretreatment of VSMCs with p38 MAPK inhibitors,SB203580 and SB202190, dose-dependently inhibited chylomicron remnants-induced MCP-1 mRNA and protein expression,whereas a MAPK kinase inhibitor (PD98059) had no effect on these responses. Chylomicron remnants-induced MCP-1 secretion into the media was much more pronounced than those induced by chylomicrons, oxidized low-density lipoproteins, or lysophosphatidylcholine. Ohylomicron remnants may exacerbate atherosclerosis by inducing endothelial cell apoptosis and stimulating MCP-1 expression in VSMCs. Less
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