Abstract
The influence of lipid composition and physical state on the rate of cholesteryl ester clearance from cytoplasmic inclusions has been investigated. Our findings demonstrate that the increased rate of clearance correlates with an increased cellular triglyceride content and a more fluid cholesteryl ester physical state. Cultured rat hepatoma cells were induced to accumulate esterified cholesterol in a smectic liquid-crystalline state by exposure to free cholesterol-rich phospholipid dispersions. Addition of cis-unsaturated fatty acids to this loading medium (either oleate, linoleate, linolenate, or eicosadienoate) resulted in a substantial increase in cellular triglyceride content (greater than 7 times non-fatty acid-treated), cellular cholesteryl esters in a liquid state, and a rate of cholesteryl ester clearance twice that of control (approximately 34% versus 17% in 12 h). In studies with oleic acid, storage of cellular cholesteryl esters in a liquid state was found to be dependent on the presence of triglycerides, and the rate at which these cells hydrolyzed cholesteryl esters was proportional to triglyceride levels. Cells exposed to either linoleic or linolenic acid hydrolyzed cholesteryl esters at the faster rate, but in contrast to findings with oleate and eicosadienoate, the storage of cholesteryl esters in a liquid state may also be a consequence of the modified fatty acyl composition of the cholesteryl esters themselves. Addition of a saturated fatty acid (palmitate) or a fatty acid with a trans-double bond (elaidate) to the cholesterol loading media had little effect on cellular triglyceride content, cholesteryl ester physical state, or the rate of cholesteryl ester clearance.
Highlights
The influence of lipid composition and physical state on the rate of cholesteryl ester clearance from cytoplasmic inclusions has been investigated
To further understand the relationships among cellular lipid composition, inclusion physical state, and clearance of esterified cholesterol, a seriesof experiments were conducted in which cells were induced to store cholesteryl ester in the presence of differing concentrations of oleic acid
Examination of the fatty acyl composition of cholesteryl esters demonstrates that cholesteryl oleate content increased linearlyfrom approximately 38 to 57% as the exogenous oleic acid concentration was increased from 0 to 40 pg/ml (Fig. 1A)
Summary
Atherosclerosis is associated with an accumulation of lipid in lesions lining the walls of large arteries. Progression of the disease is marked by a focal thickening of arterial walls and an increase in content of phospholipids, cholesterol, triglycerides, and most notably, cholesteryl esters (1-7). Characteristic foam cells form within these lesions, which are distinguished by the presence of large cholesteryl ester-rich cytoplasmic lipid droplets. 70-80% of the cholesteryl esters stored in theselesions are cholesteryl oleate and cholesteryl linoleate (1-6). Examination of atherosclerotic lesions under polarizing ”. $ Present address, Department of Pathology, Bowman GreySchool of Medicine, Winston-Salem, NC 27104. § T o whom correspondence and reprint requests should be addressed
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