Altered Endothelial Nitric Oxide Signaling as a Paradigm for Maternal Vascular Maladaptation in Preeclampsia

Preeclampsia (VD Garovic, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Preeclampsia


Purpose of Review

The goal of this review is to present the newest insights into what we view as a central failure of cardiovascular adaptation in preeclampsia (PE) by focusing on one clinically significant manifestation of maternal endothelial dysfunction: nitric oxide signaling. The etiology, symptoms, and current theories of the PE syndrome are described first, followed by a review of the available evidence, and underlying causes of reduced endothelial nitric oxide (NO) signaling in PE.

Recent Findings

PE maladaptations include, but are not limited to, altered physiological stimulatory inputs (e.g., estrogen; VEGF/PlGF; shear stress) and substrates (L-Arg; ADMA), augmented placental secretion of anti-angiogenic and inflammatory factors such as sFlt-1 and Eng, changes in eNOS (polymorphisms, expression), and reduced bioavailability of NO secondary to oxidative stress.


PE is a complex obstetrical syndrome that is associated with maternal vascular dysfunction. Diminished peripheral endothelial vasodilator influence in general, and of NO signaling specifically, are key in driving disease progression and severity.


Preeclampsia Nitric oxide Nitric oxide synthase Vascular tone Endothelial dysfunction Vasodilation, 





Asymmetric dimethyl arginine


Angiotensin type 1 receptor


Angiotensin type 2 receptor






Cyclic guanosine 3′,5′ monophosphate


Dimethylarginine dimethylaminohydrolase


Endothelin converting enzyme


Endothelium-derived hyperpolarizing factor


Endothelium-derived relaxing factor




Endothelin A receptor


Endothelin B receptor


Endothelial nitric oxide synthase


Estrogen receptor-α


Estrogen receptor-ß


Estrogen-related receptor ϒ


Flavin adenine dinucleotide


Flow-mediated dilation


Flavin mononucleotide


Gi-coupled receptor


G-protein-coupled estrogen receptor


Heme oxygenase-1


Cytokine-inducible nitric oxide synthase


Neuronal nitric oxide synthase




Lectin-like oxidized LDL receptor-1


Nicotinamide adenine dinucleotide phosphate


Nitric oxide


Oxidized low-density lipoproteins


Purinergic G protein-coupled receptor




Placental growth factor


S-adenylmethionine-dependent methyltransferase


Reactive oxygen species


Reduced uterine perfusion pressure


Soluble endoglin


Soluble fms-like tyrosine kinase-1 receptor


Silent mating-type information regulation 2 homolog 1


Superoxide dismutases


Syncytiotrophoblast extracellular vesicle


Transient receptor potential cation channel subfamily V member 1


Transient receptor potential cation channel subfamily V member 4


Vascular endothelial growth factor


VEGF receptor 1, Flt1


VEGF receptor 2, KDR


Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of Obstetrics, Gynecology and Reproductive SciencesUniversity of Vermont College of MedicineBurlingtonUSA
  2. 2.Department of Biology, Ecology and Earth ScienceUniversity of CalabriaCosenzaItaly

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