DOWN-REGULATION OF HORMONE-SENSITIVE LIPASE IN STEROL ESTER-LADEN J774.2 MACROPHAGES

The development of atherosclerotic plaques in arteries is a key step i n atherogenesis, with cholesterol ester accumulation in macrophage-der ived foam cells being recognized as a major pathogenic event in this p rocess. In this study, the mouse macrophage cell line J774.2 was induc ed to accumulate intracellular sterol eaters by incubation with 25-hyd roxycholesterol in the presence of oleic acid. The accumulation of ste rol eaters in these cells was found to be accompanied by a marked decr ease in the activity of the enzyme responsible for their hydrolysis, n amely hormone-sensitive lipase (HSL); Western blotting studies reveale d a corresponding decrease in the levels of the HSL polypeptide. Simil ar findings were obtained after incubation with oxidized low-density l ipoprotein or very-low-density lipoprotein. These findings suggest tha t down-regulation of the expression of HSL is important in cholesterol ester accumulation in macrophages.