J. Neugarten et al., ESTRADIOL INHIBITS MESANGIAL CELL-MEDIATED OXIDATION OF LOW-DENSITY-LIPOPROTEIN, The Journal of laboratory and clinical medicine, 126(4), 1995, pp. 385-391
Citations number
35
Categorie Soggetti
Medical Laboratory Technology","Medicine, General & Internal
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.