Cholesterol metabolism in glomerular cells: effect of lipoproteins from nephrotic patients

Although hyperlipidemia is a well recognized complication of the nephrotic syndrome, the precise metabolism of human lipoproteins by human glomerular cells and the effects of abnormalities in lipid and protein composition on this process have not been defined. This study examined the effects of apoB-100 containing low-density-lipoprotein (LDL) and apo B,E, containing intermediate-density lipoprotein (IDL), isolated from patients with the nephrotic syndrome (n = 6), on intracellular sterol synthesis and cholesterol esterification by human glomerular epithelial and mesangial cells. For comparison studies, human skin fibroblasts and Hep G2 cells were used. In the patients, serum LDL cholesterol level was increased threefold and IDL tenfold as compared to healthy subjects. LDL of nephrotic patients showed no differences in lipid/protein composition as compared to control LDL but IDL contained 58% more cholesterol than IDL from healthy controls. Therefore, nephrotic and control LDL showed identical inhibition of intracellular sterol synthesis and similar cholesteryl ester formation in all the four cell types. In contrast, cholesterol-rich IDL of nephrotic patients suppressed intracellular sterol synthesis more effectively than control IDL. The cholesterol esterification rate of IDL from patients was enhanced three fold on average as compared to control IDL. The various cell types differed in their rate of LDL esterification. The data indicate that the enhanced inhibition of intracellular sterol synthesis and cholesterol esterification by apo E-containing cholesterol-ester-rich IDL, which accumulate in nephrotic patients, may render these lipoproteins possible candidates for glomerular lipid deposition and progressive renal injury.