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Estrogen‐dependent methylation of sEH gene in mesenteric arteries of mice
Author(s) -
Huang An,
Sun Dong
Publication year - 2013
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.27.1_supplement.902.11
Subject(s) - epoxide hydrolase 2 , medicine , enos , endocrinology , mesenteric arteries , estrogen , blood pressure , chemistry , dna methylation , methylation , gene expression , nitric oxide , gene , artery , nitric oxide synthase , enzyme , biochemistry
Roles of soluble epoxide hydrolase (sEH) inhibitors in the regulation of blood pressure were assessed by feeding both genders’ eNOS‐KO mice with t‐TUCB (1mg/Kg, sEH inhibitor) via oral gavage for three‐weeks. There was a significant reduction in blood pressure in male t‐TUCB‐treated compared to vehicle‐treated eNOS‐KO mice, revealing an EET‐dependent prevention of hypertension. However, t‐TUCB did not significantly affect blood pressure in female eNOS‐KO mice. To this end, we hypothesized that there is a gender difference in the vascular expression of sEH, in which estrogen downregulates sEH gene via DNA methylation in the promoter region of Ephx2. Thus, mesenteric arteries isolated from male mice were incubated with physiological concentrations of 17β‐ or 17α‐estradiol (E 2 ) for 24 hours. 17β‐E 2 dose‐dependently increased DNA methylation that however, was not affected by 17α‐E 2 , indicating an estrogen‐specific response. As a result, sEH mRNA was attenuated significantly by ~60% compared to controls. Consistently, sEH protein expression was also greatly reduced in vessels of female compared to male mice. These results provide explanation for the lack of hypotensive effect in response to the treatment with sEH inhibitors in females. This is due to the in vivo presence of estrogen‐dependent inhibition of vascular sEH. (This work was supported by NIH HL‐070653)