Abstract 9012: Ablation of Neutral Cholesterol Ester Hydrolase 1 Accelerates Oxysterol-induced Macrophage Apoptosis by Aggravating Endoplasmic Reticulum Stress.

An excess of cholesterol and/or oxysterols induces apoptosis in macrophages, contributing to the development of advanced atherosclerotic lesions. In foam cells, these sterols are stored in esterified forms, which are mainly hydrolyzed by two enzymes: neutral cholesterol ester hydrolase 1 (Nceh1) and hormone-sensitive lipase (Lipe). A deficiency in either enzyme leads to accelerated growth of atherosclerotic lesions in mice. However, it is poorly understood how the esterification and hydrolysis of sterols are linked to apoptosis. While attempting to examine the intracellular structures of the Nceh1-deficient macrophages using transmission electron microscopy, we found the characteristic features of apoptosis such as condensed nuclei predominantly in Nceh1-deficient macrophages under normal culture conditions. We examined several apoptotic stimuli, and 25-hydroxycholesterol (25-HC) strikingly induced apoptosis in Nceh1-deficient macrophages (10.5% in wild-type vs 86.1% in Nceh1-deficient macrophages upon in...