title: Estradiol suppresses vascular monocyte chemotactic protein-1 expression during early atherogenesis.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Conn, USA.
authors.forename: Emre
authors.initials: E
authors.lastname: Seli
authors.forename: Umit Ali
authors.initials: UA
authors.lastname: Kayisli
authors.forename: Belgin
authors.initials: B
authors.lastname: Selam
authors.forename: Meltem
authors.initials: M
authors.lastname: Seli
authors.forename: Aydin
authors.initials: A
authors.lastname: Arici
mesh_terms: D000818:Animals; D001011:Aorta / Q000737:chemistry*; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D001391:Azo Compounds; D018932:Chemokine CCL2 / Q000032:analysis*; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004396:Coloring Agents; D004343:Drug Implants; D004730:Endothelium, Vascular / Q000737:chemistry; D005260:Female; D007150:Immunohistochemistry; D008055:Lipids / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009281:Naphthalenes; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010919:Placebos; D011973:Receptors, LDL / Q000172:deficiency; D014599:Uterus / Q000033:anatomy & histology
chemical_list: D001391:Azo Compounds; D018932:Chemokine CCL2; D002791:Cholesterol, Dietary; D004396:Coloring Agents; D004343:Drug Implants; D008055:Lipids; D009281:Naphthalenes; D010919:Placebos; D011973:Receptors, LDL; D002784:Cholesterol; C016118:Sudan Black B