title: 17-β Estradiol reduces atherosclerosis without exacerbating lupus in ovariectomized systemic lupus erythematosus-susceptible LDLr(-/-) mice.
abstract: OBJECTIVE
  To test the hypothesis that estrogen treatment in a radiation chimera mouse model of systemic lupus erythematosus (SLE) and atherosclerosis will increase SLE-associated atherosclerosis by increasing autoantibody production and inflammation.
  
  
  METHODS
  We used a radiation chimera mouse model in which bone marrow from the polygenic B6.Sle1.2.3 model of SLE was transferred to the low density lipoprotein receptor knock out (LDLr(-/-)) model of atherosclerosis on a C57BL/6 background (Sle/LDLr(-/-)). Ovariectomized chimeric mice were treated for 10 weeks with either 5.6 μg/day of 17β-estradiol or placebo; outcomes included atherosclerosis plaque size, anti-dsDNA autoantibody production and renal pathology.
  
  
  RESULTS
  Mean atherosclerosis plaque size was 67.4 ± 7.6% smaller in the estrogen treated group (p < 0.0001). Estrogen treated Sle/LDLr(-/-) mice had no significant difference in serum cholesterol concentration, lipoprotein distribution, anti-dsDNA autoantibody concentration, antibody isotype concentration and renal histopathology score compared to placebo. However, they had significantly lower mean urine protein to urine creatinine ratio (UP:UC). There was no correlation between atherosclerosis lesion size and either the renal histology score or UP:UC ratio in Sle/LDLr(-/-) mice.
  
  
  CONCLUSIONS
  These results indicate that 17β-estradiol is atheroprotective within the context of murine SLE independent of changes in serum cholesterol concentration, autoantibody concentration, or renal pathology. The SLE phenotype in Sle/LDLr(-/-) mice is not exacerbated by exogenous 17β-estradiol administration, and the reduced UP:UC ratio suggests a protective effect against lupus nephritis.
authors: Department of Pathology, Section on Comparative Medicine, Medical Center Blvd., Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. kathryn.a.shelton@gmail.com
authors: K A
authors: KA
authors: Shelton
authors: J M
authors: JM
authors: Cline
authors: J A
authors: JA
authors: Cann
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism*; D001323:Autoantibodies / Q000097:blood; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000652:urine; D004195:Disease Models, Animal; D004958:Estradiol / Q000009:adverse effects / Q000627:therapeutic use*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D007249:Inflammation; D007668:Kidney / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010052:Ovariectomy; D011507:Proteinuria; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D001323:Autoantibodies; D004967:Estrogens; D011973:Receptors, LDL; D004958:Estradiol; D002784:Cholesterol; D003404:Creatinine
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