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动脉粥样硬化兔主动脉中低密度脂蛋白的摄取与降解:局部低密度脂蛋白修饰的作用

Uptake and degradation of low density lipoproteins in atherosclerotic rabbit aorta: role of local LDL modification.

作者信息

Wiklund O, Mattsson L, Björnheden T, Camejo G, Bondjers G

机构信息

Wallenberg Laboratory for Cardiovascular Research, Department of Medicine I, University of Gothenburg, Sweden.

出版信息

J Lipid Res. 1991 Jan;32(1):55-62.

PMID:2010694
Abstract

The uptake of native and modified low density lipoprotein (LDL) in foam cells in atherosclerotic tissue was studied in an in vitro perfusion system for rabbit aorta. Experimental atherosclerosis was induced in rabbits by a combination of cholesterol feeding and mechanical injury. The aorta was perfused in an incubation chamber. A trace-label, radioiodinated tyramine-cellobiose, was used to study cellular uptake of lipoproteins. After perfusion, the tissue was digested and cells were isolated by centrifugation in a density gradient. About 40 times more LDL per cell was accumulated in the foam cell fraction than in the smooth muscle cell fraction. When the cellular uptake of LDL and acetylated LDL (AcLDL) was compared, about 4 times more AcLDL than LDL was taken up by the foam cells, suggesting that the scavenger receptor is expressed in these cells. In a competition experiment, the uptake of LDL into foam cells was reduced by 70% when a tenfold excess of AcLDL was added. This experiment suggests that native LDL is taken up by the same mechanism as AcLDL. The accumulation of radiolabeled LDL in plaques and in foam cells was reduced by 30-55% by adding vitamin E (0.1 mg/ml) to the system. These studies show an uptake of LDL by foam cells in the atherosclerotic tissue. Furthermore, these cells seem to express the scavenger receptor. The competition experiment would suggest that native LDL is taken up by the scavenger receptor. The observation that an antioxidant, vitamin E, may decrease this uptake suggests that oxidative modification of LDL is of importance for this process.

摘要

在兔主动脉体外灌注系统中,研究了动脉粥样硬化组织中泡沫细胞对天然和修饰的低密度脂蛋白(LDL)的摄取。通过喂食胆固醇和机械损伤相结合的方法在兔子中诱导实验性动脉粥样硬化。将主动脉在孵育室中进行灌注。使用一种微量标记的放射性碘化酪胺 - 纤维二糖来研究脂蛋白的细胞摄取。灌注后,消化组织并通过密度梯度离心分离细胞。每个细胞在泡沫细胞部分中积累的LDL比在平滑肌细胞部分中多约40倍。当比较LDL和乙酰化LDL(AcLDL)的细胞摄取时,泡沫细胞摄取的AcLDL比LDL多约4倍,这表明这些细胞中表达了清道夫受体。在竞争实验中,当加入十倍过量的AcLDL时,LDL进入泡沫细胞的摄取减少了70%。该实验表明天然LDL与AcLDL通过相同的机制被摄取。通过向系统中添加维生素E(0.1mg/ml),放射性标记的LDL在斑块和泡沫细胞中的积累减少了30 - 55%。这些研究表明动脉粥样硬化组织中的泡沫细胞摄取LDL。此外,这些细胞似乎表达清道夫受体。竞争实验表明天然LDL被清道夫受体摄取。抗氧化剂维生素E可能会减少这种摄取的观察结果表明LDL的氧化修饰对该过程很重要。

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Uptake and degradation of low density lipoproteins in atherosclerotic rabbit aorta: role of local LDL modification.动脉粥样硬化兔主动脉中低密度脂蛋白的摄取与降解:局部低密度脂蛋白修饰的作用
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Modified low density lipoprotein isolated from atherosclerotic lesions does not cause lipid accumulation in aortic smooth muscle cells.从动脉粥样硬化病变中分离出的修饰低密度脂蛋白不会导致主动脉平滑肌细胞内脂质积聚。
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