Interactions of low density lipoprotein with rat mesangial cells

Interactions of low density lipoprotein with rat mesangial cells Hyperlipidemia may contribute to the pathogenesis of glomerular sclerosis. We therefore studied binding and uptake of low density lipoprotein (LDL) by cultured rat mesangial cells. In addition effects of LDL on PGE 2 synthesis and cell proliferation were determined. At 4°C mesangial cells bound [ 125 I] LDL in a time- and concentration-dependent manner with half-maximal binding observed at 5 µg/ml of LDL protein. Binding was blocked by excess unlabeled LDL and by heparin. Uptake (binding plus internalization) of LDL at 37°C markedly exceeded binding at 4°C, continued to increase even with longer periods of incubation, and showed no saturability, consistent with uptake of LDL by mesangial cells. Further evidence for LDL uptake by mesangial cells was obtained by use of the fluorescent probe l, 1′-dioactadecyl-3,3,3′ 3′-tetramethylindocarbocyanine perchlorate-labeled LDL (Dil-LDL). Incubation of mesangial cells with Dil-LDL at 37°C showed positive fluorescence for all mesangial cells, indicating uptake of the Dil-LDL. LDL had a biphasic effect on mesangial cell proliferation as determined by [ 3 H] thymidine incorporation. LDL at 10 µg/ml enhanced [ 3 H] thymidine uptake modestly, but significantly, whereas a progressive and marked inhibition occurred at LDL concentrations from 100 to 500 µg/ml. While LDL at 10 and 100 µg/ml significantly stimulated PGE 2 production, inhibition of PGE 2 by meclofenamate did not influence the effects of LDL on [ 3 H] thymidine incorporation. We conclude that mesangial cells show specific binding and uptake of LDL and that high concentrations of LDL markedly decrease mesangial cell proliferation. These findings may pertain to the pathogenesis of glomerular lesions in hyperlipidemia of renal disease.