he role of lipoprotein-X in the development of glomerulosclerosis in familial LCAT deficienty

Progressive glomerulosclerosis is a major complication in patients with familial lecithin:cholesterol acyltransferase (LCAT) deficiency. The absence of active LCAT in the plasma of these patients leads to the formation of an abnormal plasma lipoprotein, lipoprotein-X (Lp-X). Renal biopsies of these patients have revealed lipid deposition, macrophage infiltration, the presence of foam cells, and mesangial cell proliferation in affected glomeruli. The objective of this project was to examine the role of Lp-X in the development of glomerulosclerosis. Our results have demonstrated that Lp-X is taken up by cultured rat mesangial cells and that the lipid component of Lp-X is metabolized intracellularly. We have also investigated the role of apolipoproteins in the uptake of Lp-X. Both apo C-l and 0-1II inhibited Lp-X uptake while C-ll (1.5 fold) and E (4 fold), as well as all four apolipoproteins combined (1.5 fold), stimulated this process. We have also observed that cell surface proteoglycans are involved in modulating the uptake of this abnormal lipoprotein. Lp-X, either alone or combined with rat peritoneal macrophages, has no effect of the proliferation of mesangial cells.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofGraduat