Coexistence of foam cells and hypocholesterolemia in mice lacking the ABC transporters a1 and g1
Coexistence of foam cells and hypocholesterolemia in mice lacking the ABC transporters a1 and g1
复制标题
DOI：
10.1161/circresaha.107.161711
复制
发表时间：
2008-01-04
影响因子：
20.1
通讯作者：
Van Eck, Miranda
中科院分区：
文献类型：
--
作者：
Out, Ruud;Jessup, Wendy;Van Eck, Miranda
巨噬细胞可以成为泡沫细胞的概念被普遍接受，这是由于脂蛋白对胆固醇的摄取和胆固醇外流之间的失衡造成的。ABCA1和Abcg1是两个胆固醇转运体，可能通过顺序作用来清除细胞中的胆固醇，但目前它们在体内的联合作用尚不清楚。我们在此报道，尽管存在严重的血浆低胆固醇血症，但ABCA1和Abcg1在小鼠体内的靶向性干扰会导致组织巨噬细胞的大量脂质堆积和泡沫细胞形成。在体外观察到细胞胆固醇外流被完全消融，而在体内巨噬细胞特异性的反向胆固醇向粪便的转运显著减少。尽管组织巨噬细胞形成大量泡沫细胞，但即使在1岁大的小鼠身上也没有观察到血管壁中的脂肪堆积，这表明双基因敲除小鼠缺乏将巨噬细胞吸引到血管壁的触发因素，可能是因为他们的低胆固醇血症。综上所述，即使在低胆固醇条件下，巨噬细胞也可以转化为泡沫细胞，而ABCA1和Abcg1在防止泡沫细胞形成方面发挥着重要作用。
The concept that macrophages can become foam cells as a result of a disturbed balance between the uptake of cholesterol from lipoproteins and cholesterol efflux is generally accepted. ABCA1 and ABCG1 are two cholesterol transporters that may act sequentially to remove cellular cholesterol, but currently their combined role in vivo is unknown. We report here that targeted disruption of both ABCA1 and ABCG1 in mice, despite severe plasma hypocholesterolemia, leads to massive lipid accumulation and foam cell formation of tissue macrophages. A complete ablation of cellular cholesterol efflux in vitro is observed, whereas in vivo macrophage-specific reverse cholesterol transport to the feces is markedly decreased. Despite the massive foam cell formation of tissue macrophages, no lipid accumulation was observed in the vascular wall, even in mice of 1 year old, indicating that the double knockout mice, possibly because of their hypocholesterolemia, lack the trigger to attract macrophages to the vessel wall. In conclusion, even under hypocholesterolemic conditions macrophages can be converted into foam cells, and ABCA1 and ABCG1 play an essential role in the prevention of foam cell formation.