title: Heme Oxygenase-1 Attenuates Hypoxia-Induced sFlt-1 and Oxidative Stress in Placental Villi through Its Metabolic Products CO and Bilirubin.
abstract: One of the most prevalent complications of pregnancy is preeclampsia, a hypertensive disorder which is a leading cause of maternal and perinatal morbidity and premature birth with no effective pharmacological intervention. While the underlying cause is unclear, it is believed that placental ischemia/hypoxia induces the release of factors into the maternal vasculature and lead to widespread maternal endothelial dysfunction. Recently, HO-1 has been shown to downregulate two of these factors, reactive oxygen species and sFlt-1, and we have reported that HO-1 induction attenuates many of the pathological factors of placental ischemia experimentally. Here, we have examined the direct effect of HO-1 and its bioactive metabolites on hypoxia-induced changes in superoxide and sFlt-1 in placental vascular explants and showed that HO-1 and its metabolites attenuate the production of both factors in this system. These findings suggest that the HO-1 pathway may be a promising therapeutic approach for the treatment of preeclampsia.
authors.affiliation: Department of Physiology and Biophysics and Center for Excellence in Cardiovascular-Renal Research, The University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: George
authors.forename: Drew
authors.initials: D
authors.lastname: Colson
authors.forename: Jeremy
authors.initials: J
authors.lastname: Dixon
authors.forename: Ana C
authors.initials: AC
authors.lastname: Palei
authors.forename: Joey P
authors.initials: JP
authors.lastname: Granger