In vitro lipid peroxidation of LDL from postmenopausal cynomolgus macaques treated with female hormones

Premenopausal women and postmenopausal women given estrogen are protected from cardiovascular diseases compared with men. Previous studies investigated whether estrogen treatment protects low density lipoprotein (LDL) from in vitro oxidation as a potential mechanistic explanation for the beneficial effect of estrogen. Results of these studies are mixed, and very few studies considered aspects of LDL that influence LDL oxidation. This study investigated whether treating postmenopausal female cynomolgus macaques with conjugated equine estrogens (CEE), medroxyprogesterone acetate (MPA), CEE + MPA, or tamoxifen, a mixed estrogen receptor agonist/antagonist, would protect LDL from in vitro oxidation. LDL was isolated from monkeys fed an atherogenic diet for 12 weeks or the same diet with CEE, MPA, CEE + MPA, or tamoxifen added at levels equivalent (on a caloric basis) to those given to women. LDL was subjected to Cu(2+) (3 micromol/L) or 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH, 1 mmol/L) and LDL oxidation was determined by the lag time before rapid formation of conjugated dienes and by the maximal rate of conjugated diene formation (propagation rate). Lag times and propagation rates were not affected by treatment. Lag times for Cu(2+) oxidation were related to LDL tocopherol while lag times for AAPH oxidation were related to high density lipoprotein (HDL) cholesterol and to LDL molecular weight. Multivariate analysis showed that LDL alpha- and gamma-tocopherol together could explain 27% of the variation in Cu(2+) mediated lag time (P < 0.005) among animals while HDL cholesterol, LDL gamma-tocopherol, and LDL molecular weight combined could explain 40% of the variation in AAPH- mediated lag time (P = 0.0006) among animals. After adjustment for these predictors, LDL lag times were not affected by treatment. In conclusion, in monkeys treated with female hormones, multiple factors influence in vitro low density lipoprotein (LDL) oxidation; future work will be needed to determine whether estrogen alters oxidation of LDL in the artery.-Schwenke, D. C., J. D. Wagner, and M. R. Adams. In vitro lipid peroxidation of LDL from postmenopausal cynomolgus macaques treated with female hormones.