Abstract 3710: Estrogen Does not Account for Accelerated Atherosclerosis in LDLr−/− Mice
Clinical studies demonstrate less atherosclerosis in pre-menopausal women compared to age-matched men, but an equalization in atherosclerosis burden and cardiovascular event rates between genders following menopause. Conversely, using the LDLR−/− mouse model we and others have previously demonstrated that young female mice develop accelerated atherosclerosis compared to age matched males. Whether this difference is due to sex hormones or differences in metabolic factors is not clear. To determine if estrogen mediated the alterations in atherosclerosis in the female mice, female mice were ovariectomized (Ovx). Ovx mice had a marked reduction in uterus weight (Sham: 86 ± 1 vs Ovx: 26 ± 1mg, P < 0.001) and both Ovx females and males had greater body weight gain when fed a lard-enriched diet (10% kcal from fat, D12451, Research Diets) for 17 weeks compared to sham females. Ovariectomy resulted in an increase in fasting glucose concentrations, which was comparable to males. Cholesterol and triglyceride concentrations were higher in both sham and Ovx females compared to males; primarily distributed in increased VLDL and LDL particles. Interestingly, ovariectomy had no significant effect on extent of atherosclerotic lesion formation in female mice and the extent of atherosclerotic lesion area in both female groups was significantly increased compared to male mice. These data suggest that gender specific differences in lipids and atherosclerotic lesion formation in female LDL-R deficient mice fed a diet enriched in lard are not mediated by estrogen.