Dipartimento di Scienze Farmacologiche, Biologiche e Chimiche Applicate, Università di Parma, 43100 Parma, Italy.
Arterioscler Thromb Vasc Biol. 2011 Jan;31(1):74-80. doi: 10.1161/ATVBAHA.110.213892. Epub 2010 Oct 21.
To assess the role of apolipoprotein (apo) E in macrophage reverse cholesterol transport (RCT) in vivo.
ApoE exerts an antiatherosclerotic activity by regulating lipoprotein metabolism and promoting cell cholesterol efflux. We discriminated between macrophage and systemic apoE contribution using an assay of macrophage RCT in mice. The complete absence of apoE lead to an overall impairment of the process and, similarly, the absence of apoE exclusively in macrophages resulted in the reduction of cholesterol mobilization from macrophages to plasma, liver, and feces. Conversely, expression of apoE in macrophages is sufficient to promote normal RCT even in apoE-deficient mice. The mechanisms accounting for these results were investigated by evaluating the first step of RCT (ie, cholesterol efflux from cells). Macrophages isolated from apoE-deficient mice showed a reduced ability to release cholesterol into the culture medium, whereas the apoB-depleted plasma from apoE-deficient and healthy mice possessed a similar capacity to promote cellular lipid release from cultured macrophages.
Our data demonstrate, for the first time to our knowledge, that apoE significantly contributes to macrophage RCT in vivo and that this role is fully attributable to apoE expressed in macrophages.
评估载脂蛋白 (apo) E 在体内巨噬细胞胆固醇逆转运 (RCT) 中的作用。
apoE 通过调节脂蛋白代谢和促进细胞胆固醇外流发挥抗动脉粥样硬化作用。我们使用小鼠巨噬细胞 RCT 测定法区分巨噬细胞和全身 apoE 的贡献。apoE 的完全缺失导致该过程的整体受损，同样，巨噬细胞中仅缺乏 apoE 也会导致胆固醇从巨噬细胞向血浆、肝脏和粪便的动员减少。相反，即使在 apoE 缺陷小鼠中，巨噬细胞中 apoE 的表达也足以促进正常的 RCT。通过评估 RCT 的第一步（即细胞内胆固醇外排）来研究这些结果的机制。从 apoE 缺陷小鼠中分离出的巨噬细胞显示出将胆固醇释放到培养基中的能力降低，而来自 apoE 缺陷和健康小鼠的载脂蛋白 B 耗尽的血浆具有相似的促进培养的巨噬细胞释放细胞脂质的能力。
我们的数据首次证明，apoE 显著促进体内巨噬细胞 RCT，并且这种作用完全归因于巨噬细胞中表达的 apoE。
