ESTRADIOL INHIBITS MESANGIAL CELL-MEDIATED OXIDATION OF LOW-DENSITY-LIPOPROTEIN

It has been suggested that hyperlipidemia may contribute to the progre ssion of renal disease via the deleterious effects of oxidized low-den sity lipoprotein (LDL) on the glomerular mesangium. Because estrogens possess potent antioxidant activity, we sought to determine whether se x hormones influence the oxidation of LDL by mesangial cells. Rat mesa ngial cells were incubated with LDL (200 mu g/ml), and the extent of l ipid oxidation was assessed by the generation of thiobarbituric acid r eactive substances (TBARS), by increased electrophoretic mobility, and by enhanced uptake of mesangial cell-modified LDL by macrophages. A p rogressive rise in TEARS and an increase in electrophoretic mobility w as observed on incubation of LDL with mesangial cells. Coincubation wi th estradiol (10 mu mol/L) reduced TEARS generation by 46% at 36 hours (p < 0.01) and reversed the increase in relative electrophoretic mobi lity (1.25 +/- 0.07 vs 1.01 +/- 0.03, p < 0.05). LDL that had been oxi dized by mesangial cells in the presence of estradiol (10 mu mol/L) sh owed reduced uptake by macrophages when compared with LDL that had bee n oxidized by mesangial cells in the absence of estradiol (14 +/- 2 pm ol/10(6) cells per hour vs 22 +/- 3 pmol/10(6) cells per hour, p < 0.0 5). In contrast, neither testosterone nor estrone had any effect on th ese parameters. We conclude that estradiol, by virtue of its antioxida nt properties, inhibits mesangial cell-mediated oxidation of LDL and r educes the uptake of mesangial cell-modified LDL by macrophages.