Jepson C A, Harrison J A, Kraemer F B, Yeaman S J
Department of Biochemistry and Genetics, Medical School, University of Newcastle upon Tyne, UK.
Biochem J. 1996 Aug 15;318 ( Pt 1)(Pt 1):173-7. doi: 10.1042/bj3180173.
The development of atherosclerotic plaques in arteries is a key step in atherogenesis, with cholesterol ester accumulation in macrophage-derived foam cells being recognized as a major pathogenic event in this process. In this study, the mouse macrophage cell line J774.2 was induced to accumulate intracellular sterol esters by incubation with 25-hydroxycholesterol in the presence of oleic acid. The accumulation of sterol esters in these cells was found to be accompanied by a marked decrease in the activity of the enzyme responsible for their hydrolysis, namely hormone-sensitive lipase (HSL); Western blotting studies revealed a corresponding decrease in the levels of the HSL polypeptide. Similar findings were obtained after incubation with oxidized low-density lipoprotein or very-low-density lipoprotein. These findings suggest that down-regulation of the expression of HSL is important in cholesterol ester accumulation in macrophages.
动脉粥样硬化斑块的形成是动脉粥样硬化发生过程中的关键步骤，巨噬细胞源性泡沫细胞中胆固醇酯的积累被认为是这一过程中的主要致病事件。在本研究中，小鼠巨噬细胞系J774.2在油酸存在的情况下与25-羟基胆固醇孵育，诱导细胞内固醇酯积累。发现这些细胞中固醇酯的积累伴随着负责其水解的酶即激素敏感性脂肪酶（HSL）活性的显著降低；蛋白质印迹研究显示HSL多肽水平相应降低。用氧化低密度脂蛋白或极低密度脂蛋白孵育后也得到了类似的结果。这些发现表明，HSL表达的下调在巨噬细胞胆固醇酯积累中起重要作用。
