CHOLESTEROL-METABOLISM IN GLOMERULAR CELLS - EFFECT OF LIPOPROTEINS FROM NEPHROTIC PATIENTS

Although hyperlipidemia is a well recognized complication of the nephr otic syndrome, the precise metabolism of human lipoproteins by human g lomeru lar cells and the effects of abnormalities in lipid and protein composition on this process have not been defined. This study examine d the effects of apoB-100 containing low-densily-lipoprotein (LDL) and apo B,E containing inter mediate-density lipoprotein (IDL), isolated from patients with the nephrotic syndrome (n=6), on intracellular ster ol synthesis and cholesterol esterification by human glomerular epithe lial and mesangial cells. For comparison studies, human skin fibroblas ts and Hep G(2) cells were used. In the patients, serum LDL cholestero l level was increased threefold and IDL tenfold as compared to healthy subjects. LDL of nephrotic patients showed no differences in lipid/pr otein composition as compared to control LDL but IDL contained 58% mor e cholesterol than IDL from healthy controls. Therefore, nephrotic and control LDL showed identical inhibition of intracellular sterol synth esis and similar cholesteryl ester formation in all the four cell type s. 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 yenhanced thr ee fold on average as compared to control IDL. The various cell types differed in their rate of LDL esterification. The data indicate that t he enhanced inhibition of intracellular sterol synthesis and cholester ol esterification by apo E-containing cholesterol-ester-rich IDL, whic h accumulate in nephrotic patients, may render these lipoproteins poss ible candidates for glomerular lipid deposition and progressive renal injury.