title: Relationship between hypoxia and downstream pathogenic pathways in preeclampsia.
abstract: Defects in angiogenesis and mitochondrial function in the placenta contribute to the pathogenesis of preeclampsia; however upstream regulators of these pathways are not known. It has been argued that placental hypoxia secondary to abnormal spiral artery remodeling may play a causal role in the angiogenic and mitochondrial abnormalities noted in preeclampsia. The aim of this study was to evaluate the relationship between hypoxia-inducible factor-1α (HIF-1α) ¸ a surrogate of hypoxia, and soluble fms-tyrosine kinase 1 (sFlt1), a circulating anti-angiogenic factor, and microRNA 210 (miR-210), a microRNA that regulates mitochondrial function, in human placentas from preeclamptic and non-hypertensive pregnancies. We first confirmed a 2.5-fold upregulation of HIF-1α protein in placentas from preeclampsia when compared to non-hypertensive controls. Consistent with prior studies, we also observed a 10-fold upregulated sFlt1 mRNA and 2-fold upregulated miR-210 in preeclamptic tissue. Interestingly, while sFlt1 mRNA correlated with miR-210 in preeclampsia (R2= 0.77, p = 0.0004), there were no significant correlations between these molecules and HIF1α expression. We conclude that non-hypoxia pathways may be involved in the abnormal angiogenic and metabolic alterations noted in preeclampsia.
authors.affiliation: a Departments of Medicine, Obstetrics and Gynecology, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , Massachusetts , USA.|b Department of Obstetrics , Federal University of São Paulo , São Paulo , Brazil.
authors.forename: Henri Augusto
authors.initials: HA
authors.lastname: Korkes
authors.affiliation: b Department of Obstetrics , Federal University of São Paulo , São Paulo , Brazil.
authors.forename: Leandro
authors.initials: L
authors.lastname: De Oliveira
authors.affiliation: b Department of Obstetrics , Federal University of São Paulo , São Paulo , Brazil.
authors.forename: Nelson
authors.initials: N
authors.lastname: Sass
authors.affiliation: a Departments of Medicine, Obstetrics and Gynecology, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , Massachusetts , USA.
authors.forename: Saira
authors.initials: S
authors.lastname: Salahuddin
authors.affiliation: a Departments of Medicine, Obstetrics and Gynecology, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , Massachusetts , USA.
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.affiliation: a Departments of Medicine, Obstetrics and Gynecology, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston , Massachusetts , USA.
authors.forename: Augustine
authors.initials: A
authors.lastname: Rajakumar
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000150:complications; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000209:etiology / Q000378:metabolism*; D011247:Pregnancy; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C543800:MIRN210 microRNA, human; D035683:MicroRNAs; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: HIF-1α protein; miR-210; placenta; preeclampsia; pregnancy; sFlt1