Objective: This study was undertaken to determine whether estrogen down-regulates vascular monocyte chemotactic protein-1 expression during the development of atherosclerosis in vivo and to identify the cellular localization of monocyte chemotactic protein-1 expression under baseline conditions and in response to atherogenic stimuli.
Study design: Female, homozygous low-density lipoprotein-receptor-deficient mice (n = 68) in a C57BL/6 background underwent ovariectomy, were implanted subcutaneously with 17beta-estradiol or placebo pellets, and were changed to a high cholesterol (1.25%) diet. Thereafter, four mice from each group were killed weekly for 8 weeks, and their aortae were frozen for immunohistochemical analysis. The lipid deposition was identified by Sudan black B staining. Monocyte chemotactic protein-1 expression was detected with a rabbit anti-mice monocyte chemotactic protein-1 antibody, and semiquantitative analysis was performed.
Results: Consistent with previous reports, estradiol resulted in diminished vascular lipid deposition (22% +/- 7% vs 15% +/- 6% at 8 weeks of gestation, P <.05). We found that the inhibition of lipid deposition in aortae of animals that were treated with estrogen is associated with a concomitant down-regulation of monocyte chemotactic protein-1 immunoreactivity in aortic endothelial and smooth muscle cells (P <.05). Serum total cholesterol concentrations did not differ between the two treatment groups, which suggests a direct effect of estradiol on the aorta.
Conclusion: Our findings suggest that one of the mechanisms by which estrogen down-regulates atherogenesis is by the suppression of vascular monocyte chemotactic protein-1 expression, which leads to decreased macrophage recruitment to the arterial wall early in the process.