Low level expression of hormone-sensitive lipase in arterial macrophage-derived foam cells: potential explanation for low rates of cholesteryl ester hydrolysis

Conversion of arterial macrophages into foam cells is a key process involve d in both the initiation and progression of atherosclerotic lesions. Foam c ell formation involves the progressive accumulation and storage of lipoprot ein-derived cholesteryl esters. The resulting imbalance in cholesterol meta bolism in arterial foam cells may be due in part to an inadequately low lev el of cytoplasmic neutral cholesteryl ester hydrolase (NCEH) activity. In t his study, we have demonstrated that hormone-sensitive lipase (HSL) mRNA is expressed at very low levels in macrophage-derived foam cells, using the u nique approach of extracting mRNA from macrophage-derived foam cells purifi ed from human and rabbit atherosclerotic plaques coupled with reverse trans criptase polymerase chain reaction (RT-PCR). We also demonstrate that macro phage-derived foam cells isolated from rabbit atherosclerotic lesions exhib it a resistance to high density lipoprotein (HDL)-mediated cholesterol effl ux along with reduced levels of NCEH activity compared to lipid-loaded mous e peritoneal macrophages. Thus, low level expression of HSL may partially a ccount for the reduced NCEH activity observed in arterial foam cells isolat ed from atherosclerosis-susceptible species. (C) 2000 Elsevier Science Irel and Ltd. All rights reserved.