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

  • Preeclampsia (VD Garovic, Section Editor)
  • Published:
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Abstract

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.

Summary

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.

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Abbreviations

2-ME:

2-Methoxyestradiol

ADMA:

Asymmetric dimethyl arginine

AT1:

Angiotensin type 1 receptor

AT2:

Angiotensin type 2 receptor

BH4 :

Tetrahydrobiopterin

CaM:

Calmodulin

cGMP:

Cyclic guanosine 3′,5′ monophosphate

DDAH:

Dimethylarginine dimethylaminohydrolase

ECE:

Endothelin converting enzyme

EDH:

Endothelium-derived hyperpolarizing factor

EDRF:

Endothelium-derived relaxing factor

ET:

Endothelin

ETA :

Endothelin A receptor

ETB :

Endothelin B receptor

eNOS/NOS3:

Endothelial nitric oxide synthase

ERα:

Estrogen receptor-α

ERß:

Estrogen receptor-ß

ERRϒ:

Estrogen-related receptor ϒ

FAD:

Flavin adenine dinucleotide

FMD:

Flow-mediated dilation

FMN:

Flavin mononucleotide

Gi :

Gi-coupled receptor

GPER:

G-protein-coupled estrogen receptor

HO-1:

Heme oxygenase-1

iNOS/NOS2:

Cytokine-inducible nitric oxide synthase

nNOS/NOS1:

Neuronal nitric oxide synthase

L-Arg:

L-arginine

LOX-1:

Lectin-like oxidized LDL receptor-1

NADPH:

Nicotinamide adenine dinucleotide phosphate

NO:

Nitric oxide

oxLDL:

Oxidized low-density lipoproteins

P2Y:

Purinergic G protein-coupled receptor

PE:

Preeclampsia

PlGF:

Placental growth factor

PRMT:

S-adenylmethionine-dependent methyltransferase

ROS:

Reactive oxygen species

RUPP:

Reduced uterine perfusion pressure

sEng:

Soluble endoglin

sFlt-1:

Soluble fms-like tyrosine kinase-1 receptor

SIRT-1:

Silent mating-type information regulation 2 homolog 1

SOD:

Superoxide dismutases

STBEV:

Syncytiotrophoblast extracellular vesicle

TRPV1:

Transient receptor potential cation channel subfamily V member 1

TRPV4:

Transient receptor potential cation channel subfamily V member 4

VEGF:

Vascular endothelial growth factor

VEGFR1:

VEGF receptor 1, Flt1

VEGFR2:

VEGF receptor 2, KDR

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Authors and Affiliations

  1. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont College of Medicine, Given H.S.C. C-217A 89 Beaumont Ave, Burlington, VT, 5405, USA

    George Osol & Nga Ling Ko

  2. Department of Biology, Ecology and Earth Science, University of Calabria, Cosenza, Italy

    Maurizio Mandalà

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  1. George Osol
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  2. Nga Ling Ko
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Correspondence to George Osol.

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This article is part of the Topical Collection on Preeclampsia

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Osol, G., Ko, N.L. & Mandalà, M. Altered Endothelial Nitric Oxide Signaling as a Paradigm for Maternal Vascular Maladaptation in Preeclampsia. Curr Hypertens Rep 19, 82 (2017). https://doi.org/10.1007/s11906-017-0774-6

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