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Cholesterol Efflux Capacity of Apolipoprotein A-I Varies with the Extent of Differentiation and Foam Cell Formation of THP-1 Cells

机译:载脂蛋白A-1的胆固醇外排能力随着THP-1细胞分化和泡沫细胞形成的程度而变化

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摘要

Apolipoprotein A-I (apoA-I), the main protein component of high-density lipoprotein (HDL), has many protective functions against atherosclerosis, one of them being cholesterol efflux capacity. Although cholesterol efflux capacity measurement is suggested to be a key biomarker for evaluating the risk of development of atherosclerosis, the assay has not been optimized till date. This study aims at investigating the effect of different states of cells on the cholesterol efflux capacity. We also studied the effect of apoA-I modification by homocysteine, a risk factor for atherosclerosis, on cholesterol efflux capacity in different states of cells. The cholesterol efflux capacity of apoA-I was greatly influenced by the extent of differentiation of THP-1 cells and attenuated by excessive foam cell formation. N-Homocysteinylated apoA-I indicated a lower cholesterol efflux capacity than normal apoA-I in the optimized condition, whereas no significant difference was observed in the cholesterol efflux capacity between apoA-I in the excessive cell differentiation or foam cell formation states. These results suggest that cholesterol efflux capacity of apoA-I varies depending on the state of cells. Therefore, the cholesterol efflux assay should be performed using protocols optimized according to the objective of the experiment.
机译:载脂蛋白A-I(apoA-I)是高密度脂蛋白(HDL)的主要蛋白成分,对动脉粥样硬化具有许多保护功能,其中之一是胆固醇外流能力。尽管胆固醇外排量测定被认为是评估动脉粥样硬化发展风险的关键生物标志物,但该测定法迄今尚未得到优化。这项研究旨在调查不同状态的细胞对胆固醇外排能力的影响。我们还研究了高半胱氨酸(动脉粥样硬化的危险因素)对apoA-I修饰对不同细胞状态下胆固醇流出能力的影响。 Tpo-1细胞分化程度极大地影响了apoA-I的胆固醇外排能力,而泡沫细胞过多形成则削弱了ApoA-I的胆固醇外流能力。在优化条件下,N-高半胱氨酸化的apoA-I的胆固醇外排能力比正常apoA-I低,而在过度的细胞分化或泡沫细胞形成状态下,apoA-I之间的胆固醇外排能力没有观察到显着差异。这些结果表明,apoA-I的胆固醇外排能力根据细胞状态而变化。因此,应使用根据实验目的优化的方案进行胆固醇外流测定。

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