Oxidative stress as common trait of endothelial dysfunction in chorionic arteries from fetuses with IUGR and LGA

Schneider, Daniela; Hernández, Cherie; Farías, Marcelo; Uauy, Ricardo; Krause, Bernardo J.; Casanello, Paola

doi:10.1016/j.placenta.2015.02.003

Cited by 44 publications

(58 citation statements)

References 36 publications

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“…[51][52][53][54] It has been recently reported that one cellular response to hypoxia-ischemia is mRNA stabilization and promotion of translation through m 6 A modification of the transcription factors JUN and MYC, demonstrating that mRNA degradation is not the only effect of m 6 A. [51][52][53][54] It has been recently reported that one cellular response to hypoxia-ischemia is mRNA stabilization and promotion of translation through m 6 A modification of the transcription factors JUN and MYC, demonstrating that mRNA degradation is not the only effect of m 6 A.…”

Section: Discussionmentioning

confidence: 99%

Epitranscriptomic profiling in human placenta: N6‐methyladenosine modification at the 5′‐untranslated region is related to fetal growth and preeclampsia

et al. 2019

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Intracellular mRNA levels are not always proportional to their respective protein levels, especially in the placenta. This discrepancy may be attributed to various factors including post-transcriptional regulation, such as mRNA methylation (N6methyladenosine: m 6 A). Here, we conducted a comprehensive m 6 A analysis of human placental tissue from neonates with various birth weights to clarify the involvement of m 6 A in placental biology. The augmented m 6 A levels at the 5′-untranslated region (UTR) in mRNAs of small-for-date placenta samples were dominant compared to reduction of m 6 A levels, whereas a decrease in m 6 A in the vicinity of stop codons was common in heavy-for-date placenta samples. Notably, most of these genes showed similar expression levels between the different birth weight categories. In particular, preeclampsia placenta samples showed consistently upregulated SMPD1 protein levels and increased m 6 A at 5′-UTR but did not show increased mRNA levels. Mutagenesis of adenosines at 5′-UTR of SMPD1 mRNAs actually decreased protein levels in luciferase assay. Collectively, our findings suggest that m 6 A both at the 5′-UTR and in the vicinity of stop codon in placental mRNA may play important roles in fetal growth and disease.

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Section: Discussionmentioning

confidence: 99%

Epitranscriptomic profiling in human placenta: N6‐methyladenosine modification at the 5′‐untranslated region is related to fetal growth and preeclampsia

et al. 2019

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“…An impaired foetal growth is associated with long‐term endothelial dysfunction and vascular remodelling that can be observed as early as birth. In fact, low birthweight neonates show a reduced peripheral endothelial‐dependent relaxation, an effect that can be also observed in placental and umbilical arteries from FGR pregnancies . This impaired endothelial function is also observed in low birthweight children .…”

Section: Discussionmentioning

confidence: 83%

Adult vascular dysfunction in foetal growth‐restricted guinea‐pigs is associated with a neonate‐adult switching in Nos3 DNA methylation

et al. 2019

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Aim Foetal growth restriction (FGR) is associated with endothelial dysfunction and cardiovascular diseases in adult subjects. Early vascular remodelling and epigenetic changes occurring on key endothelial genes might precede this altered vascular function. Further, it has been proposed that oxidative stress during development may determine some of these epigenetic modifications. To address this issue, we studied the in vivo and ex vivo vascular function and Nos3 promoter DNA methylation in arteries from eight‐month‐old guinea‐pig born from control, FGR‐treated and FGR‐NAC‐treated pregnancies. Methods Femoral and carotid arteries in vivo vascular function were determined by Doppler, whilst ex vivo vascular function and biomechanical properties were assessed by wire myography. Levels of eNOS mRNA and site‐specific DNA methylation in Nos3 promoter in aorta endothelial cells (AEC) were determined by qPCR and pyrosequencing respectively. Results FGR adult showed an increased femoral vascular resistance (P < .05), stiffness (P < .05) and arterial remodelling (P < .01), along with an impaired NO‐mediated relaxation (P < .001). These effects were prevented by maternal treatment with NAC. Endothelial‐NOS mRNA levels were decreased in FGR adult compared with control and FGR‐NAC (P < .05), associated with increased DNA methylation levels (P < .01). Comparison of Nos3 DNA methylation in AEC showed a differential methylation pattern between foetal and adult guinea‐pigs (P < .05). Conclusion Altogether, these data suggest that adult vascular dysfunction in the FGR does not result from early changes in Nos3 promoter DNA methylation, but from an altered vessel structure established during foetal development.

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“…Interestingly, short‐term consequences on vascular system of the offspring can be observed at birth (Khoury et al, ). Recently, it has been reported that MO is associated with an increased vascular resistance in human umbilical arteries (Sarno et al, ), and with a diminished endothelial‐dependent relaxation of placental chorionic vessels in LGA fetuses of obese women in response to CGRP on oxidative stress conditions (Schneider et al, ), suggesting that this adverse maternal environment would produce impaired NO‐dependent vascular function in the fetoplacental unit. In this context, we found that placental chorionic arteries from LGA neonates of obese mothers present a decreased response to the vasorelaxing effects of the adiponectin receptors agonist, AdipoRon, in concordance with the reported by others.…”

Section: Discussionmentioning

confidence: 99%

“…The placental vascular tone is strongly regulated by endothelial nitric oxide (NO) produced by local NO synthase (Krause, Hanson, & Casanello, ). In support of this notion, chorionic plate arteries from LGA neonates of obese women show a decreased endothelial‐dependent relaxation in response to calcitonin‐gene related peptide (CGRP) compared to placentas of women with normal BMI (Schneider et al, ). This may be due to altered NO‐dependent vascular function related to the reported increase oxidative stress in MO.…”

Section: Introductionmentioning

confidence: 98%

LGA‐newborn from patients with pregestational obesity present reduced adiponectin‐mediated vascular relaxation and endothelial dysfunction in fetoplacental arteries

Muñoz-Muñoz

Krause

Uauy

et al. 2018

Journal Cellular Physiology

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Maternal obesity is associated with large-for-gestational-age (LGA) neonates and programming of obesity-related cardiovascular disease in the offspring, however, the mechanisms that lead to the later are unclear. Presently, interpretations of NO-dependent changes in vascular function in LGA newborn from obese mothers are conflicting. Adiponectin improves endothelial function by increasing eNOS activity and NO production. We propose that LGAs from obese mothers present a diminished vascular response to adiponectin; thus, affecting eNOS and AMPK activation. Chorionic arteries, umbilical cord and primary cultures of umbilical artery endothelial cells (HUAEC) were collected at term (>38 weeks) from uncomplicated singleton pregnancies of LGA and adequate-for-gestational (AGA) newborn. Vascular reactivity of chorionic plate arteries was assessed by wire myography. mRNA expression of adiponectin receptors 1 (AdipoR1) and AdipoR2 in HUAEC was determined by qPCR. Protein expression of AdipoR1, AdipoR2, AMPK, phospho-AMPKα , eNOS, and phospho-eNOS after stimulation with AdipoRon was determined by Western Blot. Maximal adiponectin-induced chorionic artery relaxation in LGAs was diminished compared to control. In vitro studies showed no differences in expression of AdipoRs, total AMPK and, eNOS activation between groups; however, higher expression of total eNOS and AMPK activation in HUAEC of LGA relative to AGAs were observed. LGA HUAEC showed diminished NO production and eNOS activity compared to AGA in response to AdipoRon but no changes in AMPK activation. Placental endothelium of LGAs shows a diminished vascular response to adiponectin. Moreover, eNOS activation and adiponectin-dependent NO production is lower in HUAEC of LGA from obese mothers, indicating they present dysfuncional placental-endothelial responses.

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Oxidative stress as common trait of endothelial dysfunction in chorionic arteries from fetuses with IUGR and LGA

Cited by 44 publications

References 36 publications

Epitranscriptomic profiling in human placenta: N6‐methyladenosine modification at the 5′‐untranslated region is related to fetal growth and preeclampsia

Epitranscriptomic profiling in human placenta: N6‐methyladenosine modification at the 5′‐untranslated region is related to fetal growth and preeclampsia

Adult vascular dysfunction in foetal growth‐restricted guinea‐pigs is associated with a neonate‐adult switching in Nos3 DNA methylation

LGA‐newborn from patients with pregestational obesity present reduced adiponectin‐mediated vascular relaxation and endothelial dysfunction in fetoplacental arteries

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