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Role of chylomicron remnants in vascular remodeling

乳糜微粒残余物在血管重塑中的作用

基本信息

批准号：
13670711
负责人：
ISHIKAWA Yuichi
金额：
$ 2.3万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

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 … More 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

所有形式的经皮冠状动脉介入治疗都会对血管造成损伤。动脉对损伤的反应是长期结果的基础。当进行血管成形术时，血栓、炎症、内膜和中膜夹层以及动脉壁的弹性回缩会导致新生内膜形成。乳糜微粒残留物是餐后高脂血症的主要脂蛋白，被认为是促动脉粥样硬化的脂蛋白。然而，乳糜微粒残余物增强动脉粥样硬化的机制尚未完全了解。在这里，我们研究了乳糜微粒残留对内皮细胞和平滑肌细胞的影响。我们从用鸡蛋溶液喂养的大鼠的淋巴中制备乳糜微粒，并从注射乳糜微粒的功能性肝切除大鼠的血浆中获得乳糜微粒残留物。首先，我们研究了乳糜微粒残留对人脐静脉内皮细胞（HUVECs）的影响。乳糜微粒残余物激活caspase-3活性， ...更多信息以剂量依赖性方式诱导HUVECs凋亡。接下来，我们研究了乳糜微粒残留物对培养的血管平滑肌细胞（VSMCs）中单核细胞趋化蛋白-1（MCP-1）表达的影响。MCP-1是一种趋化因子，它刺激单核细胞的迁移，在动脉粥样硬化的发展中起着关键作用。乳糜微粒残余物处理VSMC可显着增加MCP-1 mRNA和蛋白的表达，且呈时间和剂量依赖性。此外，乳糜微粒残余物激活p38丝裂原活化蛋白激酶（MAPK）和细胞外信号调节激酶（ERK 1/2）。用p38 MAPK抑制剂SB 203580和SB 202190预处理VSMCs，剂量依赖性地抑制乳糜微粒残余物诱导的MCP-1 mRNA和蛋白表达，而MAPK激酶抑制剂（PD 98059）对这些反应没有影响。乳糜微粒残余物诱导MCP-1分泌到培养基中比乳糜微粒、氧化低密度脂蛋白或溶血磷脂酰胆碱诱导的MCP-1分泌更明显。羟基微粒残留可能通过诱导内皮细胞凋亡和刺激VSMCs中MCP-1的表达而加重动脉粥样硬化。少

项目成果

期刊论文数量（20）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Takaishi H, Taniguchi T, Takahashi A, Ishikawa Y, Yokoyama M.: "High glucose accelerates MCP-1 production via p38 MAPK in vascular endothelial cells"Biochem Biophys Res Commun 2003 May 23. 305(1). 122-128

Takaishi H、Taniguchi T、Takahashi A、Ishikawa Y、Yokoyama M.：“高葡萄糖通过血管内皮细胞中的 p38 MAPK 加速 MCP-1 的产生”Biochem Biophys Res Commun 2003 年 5 月 23 日 305(1)。

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Kawashima S, Yamashita T, Ozaki M, Ohashi Y, Azumi H, Inoue N, Hirata K, Hayashi Y, Itoh H, Yokoyama M: "Endothelial NO synthase overexpression inhibits lesion formation in mouse model of vascular remodeling"Arterioscler Thromb Vasc Biol. 21(2). 201-207 (

Kawashima S、Yamashita T、Ozaki M、Ohashi Y、Azumi H、Inoue N、Hirata K、Hayashi Y、Itoh H、Yokoyama M：“内皮 NO 合酶过度表达抑制血管重塑小鼠模型中的病变形成”Arterioscler Thromb Vasc Biol。