Oxidative damage to pre-eclamptic placenta: immunohistochemical expression of VEGF, nitrotyrosine residues and von Willebrand factor

Bosco, Cleofina; González, Javier Ernesto Barreras; Gutiérrez, R.; Parra-Cordero, Mauro; Barja, P; Rodrigo, Ramón

doi:10.3109/14767058.2012.695823

Cited by 29 publications

(28 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results support evidence that there are high levels of VEGF protein [42,43], but reduced levels of mRNA [44], in placentas from preeclampsia. In this regard, although we found low protein levels of VEGF in placenta from EOPE, there were no significant changes in LOPE or preterm delivery compared to normal pregnancy.…”

Section: Discussionsupporting

confidence: 79%

Impaired A2A adenosine receptor/nitric oxide/VEGF signaling pathway in fetal endothelium during late- and early-onset preeclampsia

Escudero

Bertoglia

Hernadez

et al. 2012

Purinergic Signalling

View full text Add to dashboard Cite

To investigate whether fetal endothelial cell proliferation and migration are modulated by the A 2A adenosine receptor (A 2A AR), nitric oxide (NO) and the vascular endothelial growth factor (VEGF) signaling pathway, we isolated human umbilical vein endothelial cells from normal pregnancy (n023), preterm delivery (n04), and late-onset (LOPE, n010) and early-onset preeclampsia (EOPE, n08). We used the non-selective adenosine receptor agonist (NECA) and the selective agonist (CGS-21680) and/or selective antagonist (ZM-241385) for A 2A AR. Also, the nitric oxide synthase (NOS) inhibitor, L-NAME, was used in co-incubation with CGS-21680. Compared to normal pregnancy, EOPE exhibited low cell proliferation and migration associated with reduced expressions of A 2A AR and VEGF and NO synthesis (i.e., total and phosphorylated serine 1177 endothelial NOS and nitrite formation). In contrast, LOPE exhibited the opposite behavior in all these markers compared to normal pregnancy or EOPE. Cell proliferation and migration were increased by CGS-21680 (or NECA) in all analyzed groups (EOPE>LO-PE>normal pregnancy) compared to their respective basal conditions, an effect that was associated with high NO and VEGF synthesis and blocked by ZM-241385 with significantly different IC 50 for each group (EOPE>LOPE>normal pregnancy). The differences seem independent of gestational age.L-NAME blocked the CGS-21680-mediated cell proliferation and migration in normal pregnancy and LOPE (IC 50 036.2± 2.5 and 8.6±2.2 nM, respectively) as well as the VEGF expression in normal pregnancy. Therefore, the A 2A AR/NO/ VEGF signaling pathway exhibits a pro-angiogenic effect in normal pregnancies and LOPE, whereas impairment in this pathway seems related to the reduced angiogenic capacity of the fetal endothelium in EOPE.

show abstract

Section: Discussionsupporting

confidence: 79%

Impaired A2A adenosine receptor/nitric oxide/VEGF signaling pathway in fetal endothelium during late- and early-onset preeclampsia

Escudero

Bertoglia

Hernadez

et al. 2012

Purinergic Signalling

View full text Add to dashboard Cite

show abstract

“…In human high-altitude placentas, there are increased nitrotyrosine residues in the syncytiotrophoblast, nitrative stress and lower concentrations of anti-oxidants (Zamudio et al, 2007). These results show that hypoxia is inducing oxidative stress in placentas (Bosco et al, 2012). This is also observed in placentae from lowland women with pre-eclampsia and IUGR (Myatt et al, 2000).…”

Section: Hypoxia Umbilico-placental Deficiencies and Iugrmentioning

confidence: 57%

The placental pursuit for an adequate oxidant balance between the mother and the fetus

et al. 2014

Self Cite

View full text Add to dashboard Cite

The placenta is the exchange organ that regulates metabolic processes between the mother and her developing fetus. The adequate function of this organ is clearly vital for a physiologic gestational process and a healthy baby as final outcome. The umbilico-placental vasculature has the capacity to respond to variations in the materno-fetal milieu. Depending on the intensity and the extensity of the insult, these responses may be immediate-, mediate-, and long-lasting, deriving in potential morphostructural and functional changes later in life. These adjustments usually compensate the initial insults, but occasionally may switch to long-lasting remodeling and dysfunctional processes, arising maladaptation. One of the most challenging conditions in modern perinatology is hypoxia and oxidative stress during development, both disorders occurring in high-altitude and in low-altitude placental insufficiency. Hypoxia and oxidative stress may induce endothelial dysfunction and thus, reduction in the perfusion of the placenta and restriction in the fetal growth and development. This Review will focus on placental responses to hypoxic conditions, usually related with high-altitude and placental insufficiency, deriving in oxidative stress and vascular disorders, altering fetal and maternal health. Although day-to-day clinical practice, basic and clinical research are clearly providing evidence of the severe impact of oxygen deficiency and oxidative stress establishment during pregnancy, further research on umbilical and placental vascular function under these conditions is badly needed to clarify the myriad of questions still unsettled.

show abstract

“…Peroxynitrite is associated with biological toxic effects that are also found in pre-eclampsia (62) such as antioxidant depletion (68), deregulation of COXs (3), NOS uncoupling (58), lipid peroxidation (24), insulin resistance (52), imbalance of proand anti-inflammatory mediators (12), neuro-inflammatory disease/stroke (52), DNA damage (21), mitochondrial dysfunction (50), and renal injury associated with proteinuria and high plasma uric acid level (52). Nitrotyrosine strongly marks the vasculature of pre-eclamptic placentas (8). Recently, uric acid has been reported to mark hypertension and endothelial damage in pre-eclampsia (41).…”

Section: Discussionmentioning

confidence: 99%

Nitroso-Redox Balance and Mitochondrial Homeostasis Are Regulated bySTOX1, a Pre-Eclampsia-Associated Gene

Doridot

Châtre²,

Ducat³

et al. 2014

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Aims: Storkhead box 1 (STOX1) is a winged-helix transcription factor that is implicated in the genetic forms of a high-prevalence human gestational disease, pre-eclampsia. STOX1 overexpression confers pre-eclampsia-like transcriptomic features to trophoblastic cell lines and pre-eclampsia symptoms to pregnant mice. The aim of this work was to evaluate the impact of STOX1 on free radical equilibrium and mitochondrial function, both in vitro and in vivo. Results: Transcriptome analysis of STOX1-transgenic versus nontransgenic placentas at 16.5 days of gestation revealed alterations of mitochondria-related pathways. Placentas overexpressing STOX1 displayed altered mitochondrial mass and were severely biased toward protein nitration, indicating nitrosoredox imbalance in vivo. Trophoblast cells overexpressing STOX1 displayed an increased mitochondrial activity at 20% O 2 and in hypoxia, despite reduction of the mitochondrial mass in the former. STOX1 overexpression is, therefore, associated with hyperactive mitochondria, resulting in increased free radical production. Moreover, nitric oxide (NO) production pathways were activated, resulting in peroxynitrite formation. At low oxygen pressure, STOX1 overexpression switched the free radical balance from reactive oxygen species (ROS) to reactive nitrogen species (RNS) in the placenta as well as in a trophoblast cell line. Innovation: In pre-eclamptic placentas, NO interacts with ROS and generates peroxynitrite and nitrated proteins as end products. This process will deprive the maternal organism of NO, a crucial vasodilator molecule. Conclusion: Our data posit STOX1 as a genetic switch in the ROS/RNS balance and suggest an explanation for elevated blood pressure in pre-eclampsia. Antioxid. Redox Signal. 21, 819-834.

show abstract

Oxidative damage to pre-eclamptic placenta: immunohistochemical expression of VEGF, nitrotyrosine residues and von Willebrand factor

Cited by 29 publications

References 57 publications

Impaired A2A adenosine receptor/nitric oxide/VEGF signaling pathway in fetal endothelium during late- and early-onset preeclampsia

Impaired A2A adenosine receptor/nitric oxide/VEGF signaling pathway in fetal endothelium during late- and early-onset preeclampsia

The placental pursuit for an adequate oxidant balance between the mother and the fetus

Nitroso-Redox Balance and Mitochondrial Homeostasis Are Regulated bySTOX1, a Pre-Eclampsia-Associated Gene

Contact Info

Product

Resources

About