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

Premenopausal women and postmenopausal women given estrogen are protected f rom cardiovascular diseases compared with men. Previous studies investigate d 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 studie s considered aspects of LDL that influence LDL oxidation, This study invest igated whether treating postmenopausal female cynomolgus macaques with conj ugated 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 atheroge nic diet for 12 weeks or the same diet with GEE, MPA, CEE + MPA, or tamoxif en added at levels equivalent (on a caloric basis) to those given to women. LDL was subjected to Cu2+ (3 mu mol/L) or 2,2'-azobis(5-amidinopropane) di hydrochloride (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 r ates were not affected by treatment. Lag times for Cu2+ oxidation were rela ted to LDL tocopherol while lag times for AAPH oxidation were related to hi gh density lipoprotein (HDL) cholesterol and to LDL molecular weight, Multi variate analysis showed that LDL alpha- and gamma-tocopherol together could explain 27% of the variation in Cu2+ mediated lag time (P < 0.005) among a nimals while HDL cholesterol, LDL gamma-tocopherol, and LDL molecular weigh t combined could explain 40% of the variation in AAPH-mediated lag time (P = 0.0006) among animals. After adjustment for these predictors, LDL lag tim es were not affected by treatment. In conclusion, in monkeys treated with f emale 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.