The Role of Oxidative Stress, Adhesion Molecules and Antioxidants in Preeclampsia

Haram, Kjell; Mortensen, Jan Helge Seglem; Myking, Ole L.; Magann, Everett F.; Morrison, John C.

doi:10.2174/1573402115666190119163942

Cited by 56 publications

(41 citation statements)

References 46 publications

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“…MDA is a major metabolite of lipid peroxide breakdown and one of the first biomarkers of oxidative stress found in the maternal circulation of women with PE (Myatt and Cui, 2004;Kaur et al, 2008;Poston et al, 2011;Haram et al, 2019). Thus, the similarities of findings in hypertensive animal models, such as those used in the present study, with those described in pregnant women (Myatt and Cui, 2004;Kaur et al, 2008;Poston et al, 2011) support the use of these animal models in translational pregnancy research.…”

Section: Discussionsupporting

confidence: 67%

Grape Seed Extract Polyphenols Improve Resistance Artery Function in Pregnant eNOS–/– Mice

et al. 2020

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Hypertension during pregnancy is a leading cause of maternal and fetal morbidity and mortality worldwide, increasing the risk of complications including preeclampsia, intracerebral hemorrhage and fetal growth restriction. Increased oxidative stress is known to contribute to poor vascular function; however, trials of antioxidant supplementation have raised concerns about fetal outcomes, including risk of low birthweight. Grape seed extract polyphenols (GSEP) have been suggested to promote cardiovascular protection, at least in part through antioxidant actions. We tested the hypothesis that administration of GSEP during pregnancy would reduce oxidative stress and improve resistance artery function with no detrimental effects on fetal growth, in an established model of maternal hypertension associated with vascular dysfunction, the endothelial NO synthase knockout (eNOS −/−) mouse. Pregnant C57BL/6J (WT) and eNOS −/− mice received either GSEP (200 mg/kg/day) or drinking water, between gestational (GD) day 10.5 and GD18.5. At GD17.5, maternal systolic blood pressure (SBP) was measured; at GD18.5, maternal malondialdehyde (MDA) concentrations, vascular function of aortic, mesenteric, uterine and posterior cerebral arteries was assessed, and fetal outcome evaluated. GSEP reduced maternal SBP (P < 0.01) and plasma MDA concentrations (P < 0.01) in eNOS −/− mice. Whilst there was no effect of GSEP on vascular reactivity of aortas, GSEP improved endothelial-dependent relaxation in mesenteric and uterine arteries of eNOS −/− mice (P < 0.05 and P < 0.001, respectively) and normalized lumen diameters of pressurized posterior cerebral arteries in eNOS −/− mice (P < 0.001). Supplementation with GSEP had no effect in WT mice and did not affect fetal outcomes in either genotype. Our data suggest that GSEP improve resistance artery function, potentially through antioxidant actions, and provide a basis to further investigate these beneficial effects including in the prevention of intracerebral hemorrhage. Maternal supplementation with GSEP may be a safe intervention to improve outcomes in pregnancies associated with hypertension and vascular dysfunction.

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Section: Discussionsupporting

confidence: 67%

Grape Seed Extract Polyphenols Improve Resistance Artery Function in Pregnant eNOS–/– Mice

et al. 2020

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“…Oxidative stress is due to an excessive production of reactive oxygen and nitrogen species (Ilekis et al, ) and a reduction in the antioxidant capacity. In the pathogenesis of PE, the balance between oxidants and antioxidants is broken, being one of the key features of PE (Haram, Mortensen, Myking, Magann, & Morrison, ). Ekun et al indicated lower SOD and higher MDA levels in PE women's blood samples, suggesting the association of PE with oxidative stress (Ekun et al, ).…”

Section: Discussionmentioning

confidence: 99%

Vitexin ameliorates preeclampsia phenotypes by inhibiting TFPI‐2 and HIF‐1α/VEGF in a l‐NAME induced rat model

Zheng

Huang

et al. 2019

Drug Development Research

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Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity and mortality with few safe, effective, and minimally invasive therapeutics. Inflammation, oxidative stress, and angiogenic imbalance have been reported to contribute to PE pathogenesis. Vitexin (VI) possesses various pharmacological activities including the potent regulation of the above biological processes in different conditions. This study aims to investigate whether VI has therapeutic potential to PE and the underlying mechanisms. Sprague–Dawley pregnant rats pretreated with or without VI were fed with l‐NAME‐containing water to induce experimental PE. Results showed that VI decreased high systolic blood pressure and urinary protein in PE rats time‐ and dose‐dependently. Meanwhile, VI of higher dosage (45, 60 mg/kg) corrected abnormal pregnancy outcomes, including low pup weight and low pups/placenta ratio. In addition, VI of high dosage (60 mg/kg) decreased sFlt‐1, increased PlGF and alleviated oxidative stress both in blood and placental samples compared with nontreated PE group. Furthermore, VI alleviated placental TFPI‐2, HIF 1α, and VEGF in PE rats. In short, the present study suggests that the inhibition of placental TFPI‐2 and HIF‐1α/VEGF might be one of the potential mechanisms underlying the protective effects of VI to experimental PE induced by l‐NAME.

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“…ADM (adrenomedullin), whose expression/secretion is known to be reduced in STB from PE placentae 43 , was enriched 2.4-fold in control-over PE-iPSC derived STB. GPX3 and GPX4, members of the glutathione peroxidase family known to play crucial roles in defense against oxidative stress 16,44,45 , showed 3.6-fold and 1.5-fold higher expression, respectively, in STB derived from control-iPSC vs. PE-iPSC. Activating Transcription Factor 3 (ATF3), associated with both apoptosis and UV response gene sets, was enriched threefold in control-iPSC-derived STB.…”

Section: Global Gene Expression In Pe and Control Ipsc-derived Trophomentioning

confidence: 99%

Modeling preeclampsia using human induced pluripotent stem cells

Horii

Morey

Bui

et al. 2021

Sci Rep

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Preeclampsia (PE) is a pregnancy-specific hypertensive disorder, affecting up to 10% of pregnancies worldwide. The primary etiology is considered to be abnormal development and function of placental cells called trophoblasts. We previously developed a two-step protocol for differentiation of human pluripotent stem cells, first into cytotrophoblast (CTB) progenitor-like cells, and then into both syncytiotrophoblast (STB)- and extravillous trophoblast (EVT)-like cells, and showed that it can model both normal and abnormal trophoblast differentiation. We have now applied this protocol to induced pluripotent stem cells (iPSC) derived from placentas of pregnancies with or without PE. While there were no differences in CTB induction or EVT formation, PE-iPSC-derived trophoblast showed a defect in syncytialization, as well as a blunted response to hypoxia. RNAseq analysis showed defects in STB formation and response to hypoxia; however, DNA methylation changes were minimal, corresponding only to changes in response to hypoxia. Overall, PE-iPSC recapitulated multiple defects associated with placental dysfunction, including a lack of response to decreased oxygen tension. This emphasizes the importance of the maternal microenvironment in normal placentation, and highlights potential pathways that can be targeted for diagnosis or therapy, while absence of marked DNA methylation changes suggests that other regulatory mechanisms mediate these alterations.

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The Role of Oxidative Stress, Adhesion Molecules and Antioxidants in Preeclampsia

Cited by 56 publications

References 46 publications

Grape Seed Extract Polyphenols Improve Resistance Artery Function in Pregnant eNOS–/– Mice

Grape Seed Extract Polyphenols Improve Resistance Artery Function in Pregnant eNOS–/– Mice

Vitexin ameliorates preeclampsia phenotypes by inhibiting TFPI‐2 and HIF‐1α/VEGF in a l‐NAME induced rat model

Modeling preeclampsia using human induced pluripotent stem cells

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