Vainio Saara, Ikonen Elina
Department of Molecular Medicine, National Public Health Institute, Biomedicum Helsinki, Haartmaninkatu 8, Fl-00251 Helsinki, Finland.
Ann Med. 2003;35(3):146-55. doi: 10.1080/07853890310008198.
Mammalian cells have evolved complex feedback mechanisms to ensure sufficient supply of cholesterol and to prevent its excessive accumulation. During the process of atherosclerosis, these homeostatic mechanisms fail in macrophages. Uncontrolled cholesterol deposition is promoted by scavenger functions of the macrophages and the adaptive mechanisms elicited are not sufficient to process the lipid load. Consequently, a lipid-laden 'foam cell' is formed. In this review, we summarize key aspects of intracellular cholesterol processing in the special case of macrophages, including mechanisms of lipoprotein cholesterol uptake, fate of the internalized cholesterol and mechanisms implicated in cholesterol efflux. The importance of inflammatory cues, the cellular compartmentalization of cholesterol homeostatic responses and the increasing information on the transcriptional control of cholesterol balance are discussed.
哺乳动物细胞已经进化出复杂的反馈机制，以确保胆固醇的充足供应并防止其过度积累。在动脉粥样硬化过程中，这些稳态机制在巨噬细胞中失效。巨噬细胞的清道夫功能促进了不受控制的胆固醇沉积，并且引发的适应性机制不足以处理脂质负荷。因此，形成了充满脂质的“泡沫细胞”。在本综述中，我们总结了巨噬细胞特殊情况下细胞内胆固醇处理的关键方面，包括脂蛋白胆固醇摄取机制、内化胆固醇的命运以及与胆固醇流出有关的机制。还讨论了炎症信号的重要性、胆固醇稳态反应的细胞区室化以及关于胆固醇平衡转录控制的越来越多的信息。
