Lysosomes, cholesterol and atherosclerosis.
Lysosomes, cholesterol and atherosclerosis.
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DOI：
10.2217/clp.10.70
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发表时间：
2010-12-01
影响因子：
--
通讯作者：
Jerome WG
中科院分区：
文献类型：
--
作者：
Jerome WG
充血胆固醇的巨噬细胞泡沫细胞是动脉粥样硬化病变的重要组成部分。减少皮损中的类固醇沉积可减少临床事件。溶酶体中的类固醇积聚已被证明特别难从泡沫细胞中动员出来。此外，溶酶体中过多的类固醇积累也有不良影响，包括完全破坏溶酶体的功能。最近，我们证明了用含有甘油三酯的颗粒处理培养中充斥着类固醇的巨噬细胞可以逆转胆固醇对溶酶体的许多影响，并显著降低这些细胞中的类固醇负荷。本文描述了有关溶酶体类固醇充血的已知情况，讨论了甘油三酯产生其作用的可能机制，并评估了降低泡沫细胞中溶酶体胆固醇水平的可能的积极和消极影响。
Cholesterol-engorged macrophage foam cells are a critical component of the atherosclerotic lesion. Reducing the sterol deposits in lesions reduces clinical events. Sterol accumulations within lysosomes have proven to be particularly hard to mobilize out of foam cells. Moreover, excess sterol accumulation in lysosomes has untoward effects, including a complete disruption of lysosome function. Recently, we demonstrated that treatment of sterol-engorged macrophages in culture with triglyceride-containing particles can reverse many of the effects of cholesterol on lysosomes and dramatically reduce the sterol burden in these cells. This article describes what is known about lysosomal sterol engorgement, discusses the possible mechanisms by which triglyceride could produce its effects, and evaluates the possible positive and negative effects of reducing the lysosomal cholesterol levels in foam cells.