Large variations in human foam cell formation in individuals: a fully autologous in vitro assay based on the quantitative analysis of cellular neutral lipids

Large variations in human foam cell formation in individuals: a fully autologous in vitro assay based on the quantitative analysis of cellular neutral lipids
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DOI:
10.1016/s0021-9150(99)00268-3
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发表时间:
2000-02-01
期刊:
影响因子:
5.3
通讯作者:
Jelk, J
Jelk, J
中科院分区:
医学2区
文献类型:
--
作者:
Asmis, R;Jelk, J

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单核细胞来源的巨噬细胞转化为富含脂质的泡沫细胞是早期动脉粥样硬化病变发展过程中的一个特征和关键事件。我们调查了不同个体形成泡沫细胞的倾向是否有所不同。我们基于最近开发的一种新的人单核细胞来源的巨噬细胞(Wintergerst ES,Jelk J,Asmis,R.)的培养技术,建立了一种完全自体的泡沫细胞分析方法,并对CD14,CD36和低密度脂蛋白受体在人单核细胞来源的巨噬细胞上的差异表达进行了研究。研究巨噬细胞分化和异质性的一种新的细胞培养系统,组织化学。细胞生物。1998年;110:231-241)。用薄层层析法和激光密度法测定人巨噬细胞中胆固醇、甘油三酯和胆固醇酯的水平。通过涡旋获得的聚集的低密度脂蛋白被发现是人巨噬细胞中泡沫细胞形成的可重复刺激。在我们的手中,Cu2+氧化的低密度脂蛋白也会诱导胆固醇酯的积累,但只有在涡流的时候。我们发现,在10个月的时间里,个体中泡沫细胞的形成差异不到25%。相比之下,我们观察到8名男性志愿者在泡沫细胞形成方面的差异是7倍。将泡沫细胞转移到含有新鲜解冻的自体血清的培养液中,在1周内导致75%的消退,与细胞胆固醇酯的积累量无关。泡沫细胞的形成既与血清无关,也与细胞胆固醇和甘油三酯水平无关。因此,形成泡沫细胞的倾向可以代表个体动脉粥样硬化形成风险的新指标。(C)2000爱思唯尔爱尔兰科学有限公司。保留所有权利。
The transformation of monocyte-derived macrophages into lipid-laden foam cells constitutes a characteristic and crucial event in the development of the earliest atherosclerotic lesions. We investigated whether the propensity to form foam cells varies among individuals. We developed a fully autologous foam cell assay based on a recently developed novel culture technique for human monocyte-derived macrophages (Wintergerst ES, Jelk J, Asmis, R. Differential expression of CD14, CD36 and the LDL receptor on human monocyte-derived macrophages. A novel cell culture system to study macrophage differentiation and heterogeneity, Histochem. Cell Biol. 1998;110:231-241). Thin layer chromatography and laser densitometry were used to determine cholesterol, triglyceride and cholesteryl ester levels in human macrophages. Aggregated LDL obtained by vortexing was found to be a reproducible stimulus of foam cell formation in human macrophages. In our hands, Cu2+-oxidized LDL also induced cholesteryl ester accumulation, but only when vortexed. We found that foam cell formation in an individual varied by less than 25% over a 10-month period. In contrast, we observed a sevenfold difference in foam cell formation among eight male volunteers. The transfer of foam cells into culture medium with freshly thawed autologous serum resulted in a 75% regression within 1 week, independent of the amount of cellular cholesteryl esters accumulated. Foam cell formation correlated neither to serum nor to cellular cholesterol and triglyceride levels. The propensity to form foam cells could therefore represent a novel indicator of individual risk of atherogenesis. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.