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Effects of 17β‐estradiol replacement in a model of renal ischemia in the ovariectomized female apolipoprotein E knockout mouse (1135.2)
Author(s) -
Li Lijun,
Ji Hong,
Holloway Chelsee,
Sandberg Kathryn,
Ecelbarger Carolyn
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1135.2
Subject(s) - ovariectomized rat , medicine , endocrinology , kidney , apolipoprotein e , neointima , ischemia , renal ischemia , estrogen , reperfusion injury , restenosis , disease , stent
Cardiovascular disease is a major cause of morbidity and mortality in postmenopausal women. 17ß‐estradiol (E2) replacement in ovarian hormone deficient rodents inhibits renal and vascular damage in models of ischemia and attenuates inflammatory responses in models of atherosclerosis. We hypothesized that E2 replacement in ovariectomized (OVX) female atherosclerotic mice would protect against vasculature and kidney damage in renal ischemia by attenuating inflammation. Left renal artery incomplete ligation and ovariectomies were performed on 12‐week‐old, female apolipoprotein E (ApoE) knockout (KO) mice and either E2 (2 μg/day x 60 days) or placebo (P) pellets (n = 6/group) were inserted subcutaneously. After 60 days, animals were euthanized and kidneys, blood, and aortic and carotid vessels were obtained. E2 replacement attenuated the ischemia‐induced reduction in left kidney weight [g: OVX + E2, 0.13 ± 0.017 vs. OVX + P, 0.058 ± 0.016; p < 0.02]. E2 treatment had no effect on the contralateral right kidney weight or on body weight. E2 replacement lowered plasma insulin by 18% [µg/L: OVX + E2, 0.33 ± 0.009 vs. OVX + P, 0.40 ± 0.023; p<0.02] and plasma triglycerides by 46% [µg/dL: OVX + E2, 30.3 ± 3.5 vs. OVX + P, 56.6 ± 8.4; p<0.02]. Plasma interleukin‐6 (IL‐6) was increased by E2 [pg/ml: OVX + E2, 156 ± 67 vs. OVX + P, 16.7 ± 7.0; p<0.05]. E2 treatment attenuated the ischemia‐induced glomerular injury, tubular atrophy, interstitial fibrosis and inflammation and neointima proliferation in the thoracic and abdominal aorta and carotid artery. These findings suggest E2 markedly protects the ovarian‐hormone‐deficient atherosclerotic female from the renal and vascular damage induced by renal ischemia. Possible protective means include improvement of the metabolic profile, and a near 10X increase in mean circulating levels of the potentially anti‐inflammatory cytokine, IL‐6. Grant Funding Source : Supported by NIH DK082507 and Marriott Fellowship