Schwenke D C, Wagner J D, Adams M R
Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1072, USA.
J Lipid Res. 1999 Feb;40(2):235-44.
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.
与男性相比，绝经前女性和接受雌激素治疗的绝经后女性患心血管疾病的风险较低。以往的研究探讨了雌激素治疗是否能保护低密度脂蛋白（LDL）免受体外氧化，以此作为雌激素有益作用的潜在机制解释。这些研究结果不一，很少有研究考虑影响LDL氧化的LDL相关因素。本研究调查了用共轭马雌激素（CEE）、醋酸甲羟孕酮（MPA）、CEE + MPA或他莫昔芬（一种混合雌激素受体激动剂/拮抗剂）治疗绝经后雌性食蟹猴是否能保护LDL免受体外氧化。LDL从喂食致动脉粥样硬化饮食12周的猴子中分离出来，或者从添加了CEE、MPA、CEE + MPA或他莫昔芬的相同饮食中分离出来，添加水平（按热量计算）与给予女性的水平相当。将LDL置于Cu(2+)（3微摩尔/升）或2,2'-偶氮二异丁脒盐酸盐（AAPH，1毫摩尔/升）中，通过共轭二烯快速形成前的延迟时间和共轭二烯形成的最大速率（传播速率）来测定LDL氧化。延迟时间和传播速率不受治疗影响。Cu(2+)氧化的延迟时间与LDL生育酚有关，而AAPH氧化的延迟时间与高密度脂蛋白（HDL）胆固醇和LDL分子量有关。多变量分析表明，LDL的α-生育酚和γ-生育酚共同可以解释动物之间Cu(2+)介导的延迟时间变化的27%（P < 0.005），而HDL胆固醇、LDLγ-生育酚和LDL分子量综合起来可以解释动物之间AAPH介导的延迟时间变化的40%（P = 0.0006）。在对这些预测因素进行调整后，LDL延迟时间不受治疗影响。总之，在用女性激素治疗的猴子中，多种因素影响体外低密度脂蛋白（LDL）氧化；未来需要开展工作来确定雌激素是否会改变动脉中LDL的氧化。-施温克，D.C.，J.D.瓦格纳，和M.R.亚当斯。用女性激素治疗的绝经后食蟹猴LDL的体外脂质过氧化。
