UPTAKE AND METABOLISM OF LIPOPROTEIN-X IN MESANGIAL CELLS

Progressive glomerulosclerosis is a major complication in patients wit h familial lecithin:cholesterol acyltransferase (LCAT) deficiency. The lack of LCAT activity results in the accumulation of an abnormal lipo protein, lipoprotein-X (Lp-X), in the plasma of these patients. Lipopr otein-X contains high levels of unesterified cholesterol and phosphati dylcholine. Lp-X may play a role in the accumulation of lipids in the kidney, which in turn may lead to glomerulosclerosis. The objective of this study is to examine the uptake and metabolism of Lp-X by rat mes angial cells. Our results suggest that Lp-X is taken up by mesangial c ells and that the lipids in Lp-X are metabolized. Lysosomes containing unesterified cholesterol and phosphatidylcholine, in a molar ratio si milar to Lp-X, were synthesized to investigate the roles individual ap olipoproteins (ape CI, II, III and E) play in the uptake of Lp-X. Both apo CI and CIII inhibited its uptake while apo CII (1.5 fold) and E ( 4 fold) stimulated the uptake of Lp-X. Very low density lipoprotein (V LDL) and low density lipoprotein (LDL) inhibited Lp-X uptake by mesang ial cells. However, at higher concentrations of high density lipoprote in (HDL), the uptake of Lp-X was stimulated. Proteoglycans have an imp ortant role in regulating the uptake of Lp-X, while cytoskeleton-depen dent phagocytosis and the scavenger receptor do not appear to be invol ved.