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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-1 (HIF-1) 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-1 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 (R-2 = 0.77, p = 0.0004), there were no significant correlations between these molecules and HIF1 expression. We conclude that non-hypoxia pathways may be involved in the abnormal angiogenic and metabolic alterations noted in preeclampsia.
Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA
Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Obstet, Boston, MA USA
Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Gynecol, Boston, MA USA
Univ Fed Sao Paulo, Dept Obstet, Sao Paulo, Brazil
Sao Paulo State Univ, Botucatu Med Sch, Dept Gynecol & Obstet, Sao Paulo, Brazil
Emory Sch Med, Dept Gynecol & Obstet, Atlanta, GA USA
Sao Paulo State Univ, Botucatu Med Sch, Dept Gynecol & Obstet, Sao Paulo, Brazil