Lipid lowering reduces oxidative stress and endothelial cell activation in rabbit atheroma
Lipid lowering reduces oxidative stress and endothelial cell activation in rabbit atheroma
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DOI：
10.1161/01.cir.0000028465.52694.9b
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发表时间：
2002-09-10
期刊：
影响因子：
37.8
通讯作者：
Libby, P
中科院分区：
文献类型：
--
作者：
Aikawa, M;Sugiyama, S;Libby, P
背景-降脂可能部分通过减少血管炎症来减少患者的急性冠状动脉事件。氧化应激诱导血管细胞粘附分子1（VCAM-1）和单核细胞趋化蛋白1（MCP-1）的内皮细胞（EC）表达，并降低动脉粥样硬化保护性NO的水平，导致单核细胞募集和巨噬细胞积聚。这项研究测试的假设，降脂降低氧化应激和改善EC功能相关的炎症细胞accumulation.Methods和Results-Rabbits消耗的动脉粥样硬化饮食4个月，产生动脉粥样硬化，随后由纯化的食物饮食16个月。高胆固醇血症兔的动脉粥样硬化产生高水平的活性氧。氧化低密度脂蛋白（oxLDL）在血管细胞粘附分子-1过表达的动脉粥样硬化内皮细胞中积累。相反，动脉粥样硬化中很少有内皮细胞表达内皮型一氧化氮合酶（eNOS）。降脂降低了活性氧的产生、oxLDL的积累和抗oxLDL IgG的血浆水平。降脂后，VCAM-1和MCP-1的表达下降，eNOS表达增加，和EC表现出更正常的超微结构。这些机制可能有助于改善内皮功能和斑块稳定临床观察。
Background-Lipid lowering may reduce acute coronary events in patients in part by reducing vascular inflammation. Oxidative stress induces endothelial cell (EC) expression of vascular cell adhesion molecule 1 (VCAM-1) and monocyte chemoattractant protein 1 (MCP-1) and reduces levels of atheroprotective NO, leading to monocyte recruitment and macrophage accumulation. This study tested the hypothesis that lipid lowering decreases oxidative stress and improves EC functions related to inflammatory cell accumulation.Methods and Results-Rabbits consumed an atherogenic diet for 4 months to produce atheroma, followed by a purified chow diet for 16 months. Atherosclerotic aortas from hypercholesterolemic rabbits produced high levels of reactive oxygen species. Oxidized LDL (oxLDL) accumulated in atheroma underlying ECs that overexpress VCAM-1. In contrast, few if any ECs in atheroma stained for endothelial NO synthase (eNOS). Lipid lowering reduced reactive oxygen species production, oxLDL accumulation, and plasma levels of anti-oxLDL IgG. After lipid lowering, VCAM-1 and MCP-1 expression decreased, eNOS expression increased, and ECs exhibited a more normal ultrastructure.Conclusions-These results establish that lipid lowering can reduce oxidative stress and EC activation in vivo. These mechanisms may contribute to improvement in endothelial function and plaque stabilization observed clinically.