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，这是血管成形术时因血栓、炎症、内膜和内侧剥离以及动脉壁弹性回缩而形成的新内膜的基础。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脂蛋白。乳糜微粒残余物增强动脉粥样硬化的作用尚未完全清楚。在这里，我们研究了乳糜微粒残余物对内皮细胞和平滑肌细胞的影响，我们从喂食鸡蛋溶液的大鼠的淋巴中制备乳糜微粒，并从血浆中获得乳糜微粒残余物。首先，我们检查了乳糜微粒残留物对人脐静脉内膜细胞的影响。 (HUVEC)。乳糜微粒残余物激活 caspase-3 活性，并以剂量依赖性方式诱导 HUVEC 凋亡。接下来，我们研究了乳糜微粒残余物对培养的血管平滑肌细胞中单核细胞趋化蛋白 1 (MCP-1) 表达的影响。肌肉细胞 (VSMC) 是一种趋化因子，可刺激单核细胞迁移并在动脉粥样硬化的发展中发挥关键作用。用乳糜微粒残余物处理VSMC以时间和剂量依赖性方式显着增加MCP-1 mRNA和蛋白质的表达。此外，乳糜微粒残余物激活p38丝裂原激活蛋白激酶(MAPK)和细胞外信号调节激酶(ERK1/)。 2).用p38 MAPK抑制剂SB203580和SB202190预处理VSMC，剂量依赖性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 (PD98059) 对这些反应没有影响，乳糜微粒残余物诱导的 MCP-1 分泌到培养基中比乳糜微粒诱导的分泌更明显，氧化低。密度脂蛋白或溶血磷脂酰胆碱可能通过诱导内皮细胞凋亡和刺激而加剧动脉粥样硬化。 VSMC 中 MCP-1 的表达较少。