Premium
Heme oxygenase‐1 induction attenuates sFlt‐1 induced hypertension in pregnant rats
Author(s) -
George Eric Matthew,
Cockrell Kathy,
Arany Marietta,
Stec David E,
Granger Joey P
Publication year - 2011
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.25.1_supplement.836.7
Pregnancy induced hypertension (PIH) is one of the leading causes of fetal and maternal morbidity, affecting 5‐10% of all pregnancies, with no effective treatment. The exact etiology of the disorder is unclear, but placental ischemia has been shown to be a central causative agent. In response to placental ischemia, the antiangiogenic protein sFlt‐1, a VEGF antagonist, and reactive oxygen species are secreted, leading to the maternal syndrome. One promising therapeutic approach to treat PIH is through manipulation of the heme oxygenase‐1 (HO‐1) protein, or its two metabolites; carbon monoxide (CO), a vasodilator, and bilirubin, a powerful antioxidant. The purpose of this study was to determine whether HO‐1 induction would have beneficial effects in sFlt‐1 induced PIH. Pregnant rats were continuously infused with recombinant sFlt‐1 from gestational days 14–19, and circulating sFlt‐1 increased ~2‐fold, similar to rats with experimentally induced placental ischemia. In response, mean arterial pressure (MAP) increased 17mmHg, which was completely normalized by HO‐1 induction. Unbound circulating VEGF was decreased ~17% in response to sFlt‐1 infusion but was increased ~50% in response to HO‐1 induction. In conclusion, manipulation of HO‐1 presents an intriguing therapeutic approach to the treatment of PIH. Support for this work was provided by NIH grants HL51971 and T32 HL105324‐01.