Mechanisms of Enhanced Vascular Reactivity in Preeclampsia

Mishra, Nikita; Nugent, William H.; Mahavadi, Sunila; Walsh, Scott W.

doi:10.1161/hypertensionaha.111.176602

Cited by 49 publications

(49 citation statements)

References 47 publications

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“…An abundant literature exists on oxidant molecules associated with pre-eclampsia (48). RNS and ROS stresses are generally treated as a whole (17).…”

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

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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.

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“…An abundant literature exists on oxidant molecules associated with pre-eclampsia (48). RNS and ROS stresses are generally treated as a whole (17).…”

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

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“…Moreover, oxidative stress with H 2 O 2 has been suggested to mediate airway smooth muscle contraction by increasing intracellular Ca 2+ level and stimulating the Rho/Rho kinase pathway (Snetkov et al 2011). Mishra et al (2011) reported also that enhanced vascular reactivity of omental arteries in pre-eclampsia is attributed to ROS activation of the RhoA kinase pathway, and that the enhanced vascular reactivity is likely attributed to the infiltration of neutrophils. In addition, Shimokawa (2000) and colleagues revealed that RhoA and its downstream effector, Rho kinase, are involved in the hypercontraction of vascular smooth muscle of the coronary artery in vasospastic angina, which is probably mediated by oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Effect of oxidative stress on Rho kinase II and smooth muscle contraction in rat stomach

Al‐Shboul

Mustafa

2015

Can. J. Physiol. Pharmacol.

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Recent studies have shown that both Rho kinase signaling and oxidative stress are involved in the pathogenesis of a number of human diseases, such as diabetes mellitus, hypertension, and atherosclerosis. However, very little is known about the effect of oxidative stress on the gastrointestinal (GI) smooth muscle Rho kinase pathway. The aim of the current study was to investigate the effect of oxidative stress on Rho kinase II and muscle contraction in rat stomach. The peroxynitrite donor 3-morpholinosydnonimine (SIN-1), hydrogen peroxide (H2O2), and peroxynitrite were used to induce oxidative stress. Rho kinase II expression and ACh-induced activity were measured in control and oxidant-treated cells via specifically designed enzyme-linked immunosorbent assay (ELISA) and activity assay kits, respectively. Single smooth muscle cell contraction was measured via scanning micrometry in the presence or absence of the Rho kinase blocker, Y-27632 dihydrochloride. All oxidant agents significantly increased ACh-induced Rho kinase II activity without affecting its expression level. Most important, oxidative stress induced by all three agents augmented ACh-stimulated muscle cell contraction, which was significantly inhibited by Y-27632. In conclusion, oxidative stress activates Rho kinase II and enhances contraction in rat gastric muscle, suggesting an important role in GI motility disorders associated with oxidative stress.

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“…An excessive activation of neutrophils and monocytes in PE patients (circulating and in the decidua) have been described by many groups (21–26). These monocytes have been found to spontaneously synthesize greater amounts of pro-inflammatory cytokines such as IL-1b, IL-6, and IL-8 (27).…”

Section: Preeclampsia Development and The Immune Systemmentioning

confidence: 99%

Innate Immune System and Preeclampsia

et al. 2014

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Normal pregnancy is considered as a Th2 type immunological state that favors an immune-tolerance environment in order to prevent fetal rejection. Preeclampsia (PE) has been classically described as a Th1/Th2 imbalance; however, the Th1/Th2 paradigm has proven insufficient to fully explain the functional and molecular changes observed during normal/pathological pregnancies. Recent studies have expanded the Th1/Th2 into a Th1/Th2/Th17 and regulatory T-cells paradigm and where dendritic cells could have a crucial role. Recently, some evidence has emerged supporting the idea that mesenchymal stem cells might be part of the feto-maternal tolerance environment. This review will discuss the involvement of the innate immune system in the establishment of a physiological environment that favors pregnancy and possible alterations related to the development of PE.

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Mechanisms of Enhanced Vascular Reactivity in Preeclampsia

Cited by 49 publications

References 47 publications

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

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

Effect of oxidative stress on Rho kinase II and smooth muscle contraction in rat stomach

Innate Immune System and Preeclampsia

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