The ability to promote efflux via ABCA1 determines the capacity of serum specimens with similar high-density lipoprotein cholesterol to remove cholesterol from macrophages.
The ability to promote efflux via ABCA1 determines the capacity of serum specimens with similar high-density lipoprotein cholesterol to remove cholesterol from macrophages.
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DOI：
10.1161/atvbaha.109.199158
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发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Rothblat GH
中科院分区：
文献类型：
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作者：
de la Llera-Moya M;Drazul-Schrader D;Asztalos BF;Cuchel M;Rader DJ;Rothblat GH
我们从263个样本中测量了巨噬细胞向缺载脂蛋白血清的外排，发现具有相似HDL-C的血清的外排能力不同。因此，我们想要阐明为什么外排能力可以独立于总HDL-C或apoA-I。为了理解为什么具有相似HDL-C或apoA-I的血清在总外排能力上存在差异，我们评估了它们通过cAMP处理的J774巨噬细胞中表达的途径促进外排的能力。简单地说，巨噬细胞与Probucol预孵育以阻断ABCA1， BLT-1阻断SR-BI，并测量两种抑制剂的剩余外排。用转染的BHK-1细胞检测ABCG1外排。我们使用的是在第25和75百分位具有相似HDL-C值的标本中剔除载脂蛋白b的血清。根据总流出量高于或低于组平均水平，将每组标本分为高或低流出量。我们发现，与HDL- c无关，外排能力较高的血清中ABCA1介导的外排显著增加，这与前β-1 HDL的浓度显著相关。当这些血清基于相似的apoA-I进行类似分析时，得到了相同的结果。由于前β-1 HDL的浓度不同，具有相似HDL- c或apoA-I的血清促进巨噬细胞外排的能力不同。
We measured efflux from macrophages to apoB–depleted serum from 263 specimens and found instances where serum having similar HDL-C differed in their efflux capacity. Thus we wanted to elucidate why efflux capacity could be independent of total HDL-C or apoA-I. To understand why sera with similar HDL-C or apoA-I could differ in total efflux capacity we assessed their ability to promote efflux via the pathways expressed in cAMP treated J774 macrophages. Briefly, macrophages were pre-incubated with Probucol to block ABCA1, BLT-1 to block SR-BI and both inhibitors to measure residual efflux. ABCG1 efflux was measured with transfected BHK-1 cells. We used apoB-depleted serum from specimens with similar HDL-C values at the 25th and 75Th percentile. Specimens in each group were classified as having high or low efflux based on total efflux being above or below the group average. We found that, independently of HDL-C, sera with higher efflux capacity had a significant increase in ABCA1 mediated efflux which was significantly correlated to the concentration of preβ-1 HDL. The same result was obtained when these sera were similarly analyzed based on similar apoA-I. Sera with similar HDL-C or apoA-I differ in their ability to promote macrophage efflux due to differences in the concentration of preβ-1 HDL.