Enhanced removal of cholesterol from macrophage foam cells to serum from type IV hypertriglyceridemic subjects

Enhanced removal of cholesterol from macrophage foam cells to serum from type IV hypertriglyceridemic subjects
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DOI:
10.1016/j.atherosclerosis.2007.09.023
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发表时间:
2008-05-01
期刊:
影响因子:
5.3
通讯作者:
Fournier, Natalie
Fournier, Natalie
中科院分区:
医学2区
文献类型:
--
作者:
Attia, Nesrine;Ramaharo, Angela;Fournier, Natalie

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高胆固醇血症是一个独立的心血管危险因素,我们比较了无症状高胆固醇血症(HTG)IIb型,IV型或血脂正常(NLP)受试者的血清的潜力,以促进部分胆固醇流出和细胞胆固醇质量的变化,使用巨噬细胞泡沫细胞。将通过与乙酰化LDL孵育而负载有胆固醇的J774细胞在不存在或存在cAMP的情况下孵育以上调ABCA 1(ATP结合盒转运蛋白A1),然后与1%血清孵育24小时。与NLP相比,IV型血清表现出ABCA 1依赖性外排的主要增加,而Fib型血清表现出中等但不显著的ABCA 1介导的外排增加。此外,ABCA 1依赖性外排与血清前β-HDL或TG浓度之间呈正相关。主要发现是,与其他组相比,IV型血清诱导ABCA 1表达细胞的总胆固醇和胆固醇酯质量消耗更高。此外,总胆固醇或胆固醇酯质量变化与血清前β-HDL水平呈负相关。总之,我们第一次证明了IV型HTG受试者中高比例存在的血清前β-HDL不仅导致更高的胆固醇流出潜力,而且还增加了促进巨噬细胞泡沫细胞净清除胆固醇的能力。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
Hypertriglyceridemia being an independent cardiovascular risk factor, we have compared the potential of sera from asymptomatic hypertriglyceridemic (HTG) type IIb, type IV or normolipidemic (NLP) subjects to promote both fractional cholesterol efflux and cellular cholesterol mass changes using macrophage foam cells. The J774 cells loaded with cholesterol by incubation with acetylated LDL were incubated in the absence or presence of cAMP to upregulate ABCA1 (ATP binding cassette transporter A1) and then incubated for 24 h with 1% serum. Compared with NLP, type IV sera exhibited a major increase in ABCA1-dependent efflux while type fib sera exhibited a moderate but not significant increased ABCA1-mediated efflux. Moreover, positive correlations were established between ABCA1-dependent efflux and the serum pre beta-HDL or TG concentrations. The major finding was that the sera from type IV induced higher total cholesterol and cholesteryl ester mass depletions from ABCA1-expressing cells compared with other groups. Moreover, negative correlations were obtained between total cholesterol or cholesteryl ester mass changes and serum pre beta-HDL levels. In conclusion, we demonstrated for the first time that the serum pre beta-HDL present in high proportions in type IV HTG subjects are not only responsible for higher cholesterol efflux potential but also for increased abilities to promote net removal of cholesterol from macrophage foam cells. (c) 2007 Elsevier Ireland Ltd. All rights reserved.