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Heme oxygenase‐1 induction attenuates TNF‐α induced hypertension in pregnant rats
Author(s) -
George Eric M,
Arany Marietta,
Cockrell Kathy,
Stec David E,
Granger Joey P
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.907.2
Subject(s) - heme oxygenase , preeclampsia , medicine , endocrinology , tumor necrosis factor alpha , ischemia , in vivo , heme , placenta , pregnancy , fetus , chemistry , biology , enzyme , biochemistry , microbiology and biotechnology , genetics
Preeclampsia (PE) is a hypertensive disorder of pregnancy initiated by placental insufficiency and chronic ischemia. In response, several pathways activated in the placenta are responsible for the maternal syndrome, including increased production of the anti‐angiogenic protein sFlt‐1 and inflammatory cytokines, especially TNF‐α. Previous studies demonstrated that heme oxygenase‐1 (HO‐1) induction can block TNF‐α pathways in vitro and attenuate placental ischemia‐induced sFlt‐1 in vivo. Here, we investigated whether HO‐1 induction could attenuate TNF‐α induced hypertension in pregnant rats. In response to TNF‐α infusion (100ng/day i.p.), maternal mean arterial pressure increased vs control animals (120±4 vs 103±3 mmHg). HO‐1 induction had no effect in control animals, but significantly decreased MAP in TNF‐α infused animals (109±5 mmHg). Placental sFlt‐1 was increased by TNF‐α infusion (909±46 vs 758±45 pg/mg), which was significantly reduced by HO‐1 induction (842±102 pg/mg), suggesting a therapeutic role for HO‐1 induction in PE. Research supported by NIH grants HL105324–01, HL51971, HL088421, HL088421‐S1, and AHA grant 11POST7840039.