title: Heme oxygenase-1 in placental development and pathology.
abstract: Pregnancy is accompanied by several adaptations in the mother, such as increased blood volume, higher cardiac output and reduced peripheral vascular resistance. Inability to accomplish these changes places both her and her pregnancy at risk of major placental complications such severe pre-eclampsia (sPE) or severe intra-uterine growth restriction (sIUGR). sPE is characterized by wide-spread maternal vascular dysfunction expressed as increased systemic vascular resistance; this state is accompanied by elevated levels of anti-angiogenic factors and lower production of vasodilatory gases. One of the key molecules implicated in sPE pathogenesis is heme oxygenase-1 (HO-1), a rate-limiting enzyme that breaks down heme into carbon monoxide (CO), biliverdin and free iron. CO and bilirubin (a downstream product of biliverdin processing) account for the angiogenic, vasodilatory and anti-oxidant properties of HO-1. These collective actions of the heme breakdown metabolites generated by HO-1 offer protection against cytotoxicity, inflammation, hypoxia and other forms of cellular stress that are central to the pathogenesis of sPE. Placental HO-1 expression and exhaled CO levels are both lower in women with sPE, consistent with a pathogenic role of HO-1. In vitro experiments demonstrate that induction of HO-1 downregulates secretion of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFLT-1) and increases CO production. Advancing our understanding of regulatory pathways promoting placental HO-1 expression may offer new pharmacological tools to reduce maternal and perinatal morbidity in severe placental insufficiency syndromes, especially in women at greatest risk of developing sPE.
authors: Program in Development and Fetal Health, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Canada.
authors: K
authors: K
authors: Levytska
authors: J
authors: J
authors: Kingdom
authors: D
authors: D
authors: Baczyk
authors: S
authors: S
authors: Drewlo
mesh_terms: D000022:Abortion, Spontaneous / Q000503:physiopathology; D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism; D005260:Female; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010920:Placenta / Q000098:blood supply / Q000503:physiopathology*; D010929:Placentation; D011225:Pre-Eclampsia / Q000503:physiopathology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology
chemical_list: D002248:Carbon Monoxide; D051547:Heme Oxygenase-1