Effects of female sex hormones on LDL accumulation in the artery wall

Sex hormone replacement therapy has been shown to attenuate atherogenesis, although the mechanisms for this effect are incompletely defined. In previous studies, we showed that tumor necrosis factor-α (TNF) increased LDL accumulation in artery walls by superoxide-mediated modification of LDL. Incubation of LDL with 17-β estradiol (E₂) significantly attenuated this effect. To more carefully examine the effect of female sex hormones in the artery wall on LDL accumulation under control and oxidant stress (TNF) conditions, we implanted two-month old ovariectomized rats with 21-day release pellets containing either: 0.25mg E₂; 2.5mg E₂; 50mg progesterone(P); 50mg P⁺ 0.25mg E₂; or placebo. Carotid arteries were removed and perfused under physiological conditions. Using quantitative fluorescence microscopy, rates of fluorescently-labeled LDL accumulation were measured before and after treatment with 10ng/ml TNF. Although no significant differences between treatment groups were observed with these small sample sizes (p<.1), baseline rates of LDL accumulation were low for the 2.5mg E₂(n=5) and 0.25mg E₂(n=6) treatment groups (0.054±0.016 mV/min and 0.075±0.005 mV/min, respectively) compared to the control(n=5) and E₂+ P-implanted (n=6) groups (0.112±0.025mV/min and 0.118±0.040 mV/min, respectively). TNF treatment significantly increased LDL accumulation in all hormone treatment groups(p<.05). In conclusion, E₂ treatment tended to decrease baseline LDL accumulation rate in perfused arteries but had no effect on TNF-mediated increases in LDL accumulation. These experiments suggest incorporation of estradiol into the LDL particle may be important in preventing LDL modification and binding in the artery wall.