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The endogenous estr...
The endogenous estradiol metabolite 2-methoxyestradiol reduces atherosclerotic lesion formation in female apolipoprotein E-deficient mice
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- Fagman, Johan Bourghardt, 1980 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine,Wallenberg Laboratory for Cardiovascular Research, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden
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- Bergström, Göran, 1964 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory,Wallenberg Laboratory for Cardiovascular Research, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden
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- Krettek, Alexandra, 1968- (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory for Cardiovascular Research, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden
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- Sjöberg, Sara, 1979 (författare)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory,Wallenberg Laboratory for Cardiovascular Research, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden
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- Borén, Jan, 1963 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory,Wallenberg Laboratory for Cardiovascular Research, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden
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- Tivesten, Åsa, 1969 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Wallenberglaboratoriet,Institute of Medicine, Department of Internal Medicine,Wallenberg Laboratory,Wallenberg Laboratory for Cardiovascular Research, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden / Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg, Sweden
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(creator_code:org_t)
- Endocrine Society, 2007
- 2007
- Engelska.
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Ingår i: Endocrinology. - : Endocrine Society. - 0013-7227 .- 1945-7170. ; 148:9, s. 4128-4132
- Relaterad länk:
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https://academic.oup...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://gup.ub.gu.se...
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Abstract
Ämnesord
Stäng
- Estradiol, the major endogenous estrogen, reduces experimental atherosclerosis and metabolizes to 2-methoxyestradiol in vascular cells. Currently undergoing evaluation in clinical cancer trials, 2-methoxyestradiol potently inhibits cell proliferation independently of the classical estrogen receptors. This study examined whether 2-methoxyestradiol affects atherosclerosis development in female mice. Apolipoprotein E-deficient mice, a well-established mouse model of atherosclerosis, were ovariectomized and treated through slow-release pellets with placebo, 17beta-estradiol (6 microg/d), or 2-methoxyestradiol [6.66 microg/d (low-dose) or 66.6 microg/d (high-dose)]. After 90 d, body weight gain decreased and uterine weight increased in the high-dose but not low-dose 2-methoxyestradiol group. En face analysis showed that the fractional area of the aorta covered by atherosclerotic lesions decreased in the high-dose 2-methoxyestradiol (52%) but not in the low-dose 2-methoxyestradiol group. Total serum cholesterol levels decreased in the high- and low-dose 2-methoxyestradiol groups (19%, P < 0.05 and 21%, P = 0.062, respectively). Estradiol treatment reduced the fractional atherosclerotic lesion area (85%) and decreased cholesterol levels (42%). In conclusion, our study shows for the first time that 2-methoxyestradiol reduces atherosclerotic lesion formation in vivo. The antiatherogenic activity of an estradiol metabolite lacking estrogen receptor activating capacity may argue that trials on cardiovascular effects of hormone replacement therapy should use estradiol rather than other estrogens. Future research should define the role of 2-methoxyestradiol as a mediator of the antiatherosclerotic actions of estradiol. Furthermore, evaluation of the effects of 2-methoxyestradiol on cardiovascular disease endpoints in ongoing clinical trials is of great interest.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Other Basic Medicine (hsv//eng)
Nyckelord
- Medical sciences
- Medicin
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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