EFFECT OF LIPOPROTEINS ON CULTURED HUMAN MESANGIAL CELLS

It was recently reported that low-density lipoprotein (LDL) promotes m esangial cell proliferation, and oxidized LDL is cytotoxic for mesangi al cells, However, there have been few studies about the effects of ot her lipoproteins on mesangial cells, Accordingly, we investigated the effect of various lipoproteins on cultured human mesangial cells using H-3-thymidine (H-3-TdR) incorporation and cell counting assays, We al so investigated the levels of several cytokines in mesangial cell cult ure supernatants after stimulation by the lipoproteins, Addition of ve ry-low-density lipoprotein (VLDL) at concentrations up to 100 mu g/mL, intermediate-density lipoprotein (IDL) at up to 50 mu g/mL, and LDL a t up to 50 mu g/mL induced the proliferation of cultured human mesangi al cells, whereas cell growth was inhibited at higher concentrations, Oxidized LDL caused a concentration-dependent decrease of H-3-TdR inco rporation, High-density lipoprotein (HDL) had no proliferative effect at any concentration, Exposure to VLDL, IDL, LDL, or a high concentrat ion of HDL enhanced the secretion of interleukin-6, platelet-derived g rowth factor, and transforming growth factor-beta by mesangial cells, whereas tumor necrosis factor-alpha secretion was stimulated by oxidiz ed LDL, These findings indicate that triglyceride (TG)-rich lipoprotei ns (VLDL and IDL) promote mesangial cell proliferation as well as LDL, whereas oxidized LDL has the reverse effect, These effects of lipopro teins may be related to modulation of various cytokines. Accordingly, TO-rich lipoproteins, LDL, and oxidized LDL may be involved in mesangi al cell proliferation and injury in patients with mesangial proliferat ive glomerulonephritis. (C) 1997 by the National Kidney Foundation, In c.