Mobilization of cytoplasmic CE droplets by overexpression of human macrophage cholesteryl ester hydrolase

Journal of Lipid Research

Richard W. St. Clair¹  Shobha Ghosh²  Lawrence L. Rudel² 

[1] Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157;Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298-0050;

关键词: reverse cholesterol transport;    cholesterol efflux;    atherosclerosis;    macrophage foam cells;    cholesteryl ester;   

DOI  :  

来源: DOAJ

【 摘 要 】

The obligatory first step in the removal of cholesterol from foam cells is the hydrolysis of stored cholesteryl esters (CEs) to release free cholesterol (FC). Neutral cholesteryl ester hydrolase (CEH) catalyzes this hydrolysis, and limiting levels of CEH could play a role in determining the susceptibility to atherosclerosis. We have recently reported the first identification and cloning of cDNA for human macrophage CEH. In the present study, we tested the hypothesis that systematically varied levels of overexpression of human macrophage CEH results in a proportional degree of reduction in cellular CE content in a cell system with known and reproducible amounts of CE accumulation. CEH expression was confirmed by demonstrating the presence of CEH mRNA and protein with an increase in CEH activity. A significant reduction in intracellular lipid droplets was observed in CEH-expressing cells, together with a decrease in cellular CE mass and a 2-fold increase in FC efflux.These results demonstrate that when human macrophage CEH is expressed in lipid-laden cells, hydrolysis and mobilization of CE (stored as lipid droplets) occur. These data establish the possibility that increased CE hydrolysis, mediated by CEH up-regulation, could represent an important mechanism to reduce the cholesterol burden of foam cells.

【 授权许可】

Unknown