Effect of dietary cholesterol on rat glomerular cholesterol esterase

The accumulation of tissue cholesterol and cholesteryl esters is commonly seen during the development of both atherosclerosis and glomerulosclerosis. The intracellular cholesterol content is regulated, in part, by the hydrolysis of cholesteryl esters to cholesterol, a reaction catalyzed by cholesterol esterase. Decreased cholesterol esterase has been linked to cholesteryl ester accumulation in vascular cells and has been postulated to be an important factor in the progression of atherosclerosis and, possibly, glomerulosclerosis. In order to determine whether cholesterol esterase regulates glomerular cholesterol accumulation, the effect of cholesterol feeding on the cholesterol content and the activity of cholesterol esterase was examined in rat glomeruli. Cholesterol esterase was measured using a cholesteryl[1-14C]oleate-lecithin liposome substrate. Total and free glomerular cholesterol was measured spectrofluorometrically. Feeding rats 4% cholesterol for 2 months decreased total glomerular (acid plus neutral) cholesterol esterase activity when compared to glomeruli from similar rats fed a normal chow (1.8 +/- 0.1 versus 1.48 +/- 0.2 nmol/mg protein/h, p < 0.05). Total, free and esterified cholesterol concentrations were higher in glomeruli from cholesterol-fed rats than from controls, consistent with decreased cholesterol esterase activity. Thus, glomerular cholesterol accumulation appears to be regulated by cholesterol esterase. This finding is similar to that in other vascular tissues which have been investigated and which are prone to accumulate cholesterol during the development of atherosclerosis.