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Publication : Identification of neutral cholesterol ester hydrolase, a key enzyme removing cholesterol from macrophages.

First Author  Okazaki H Year  2008
Journal  J Biol Chem Volume  283
Issue  48 Pages  33357-64
PubMed ID  18782767 Mgi Jnum  J:143389
Mgi Id  MGI:3826763 Doi  10.1074/jbc.M802686200
Citation  Okazaki H, et al. (2008) Identification of neutral cholesterol ester hydrolase, a key enzyme removing cholesterol from macrophages. J Biol Chem 283(48):33357-64
abstractText  Unstable lipid-rich plaques in atherosclerosis are characterized by the accumulation of macrophage foam cells loaded with cholesterol ester (CE). Although hormone-sensitive lipase and cholesteryl ester hydrolase (CEH) have been proposed to mediate the hydrolysis of CE in macrophages, circumstantial evidence suggests the presence of other enzymes with neutral cholesterol ester hydrolase (nCEH) activity. Here we show that the murine orthologue of KIAA1363, designated as neutral cholesterol ester hydrolase (NCEH), is a microsomal nCEH with high expression in murine and human macrophages. The effect of various concentrations of NaCl on its nCEH activity resembles that on endogenous nCEH activity of macrophages. RNA silencing of NCEH decreases nCEH activity at least by 50%; conversely, its overexpression inhibits the CE formation in macrophages. Immunohistochemistry reveals that NCEH is expressed in macrophage foam cells in atherosclerotic lesions. These data indicate that NCEH is responsible for a major part of nCEH activity in macrophages and may be a potential therapeutic target for the prevention of atherosclerosis.
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