Cellular and Molecular Life Sciences

, Volume 71, Issue 17, pp 3219–3239

Redox regulation of endothelial cell fate

Review

Abstract

Endothelial cells (ECs) are present throughout blood vessels and have variable roles in both physiological and pathological settings. EC fate is altered and regulated by several key factors in physiological or pathological conditions. Reactive nitrogen species and reactive oxygen species derived from NAD(P)H oxidases, mitochondria, or nitric oxide-producing enzymes are not only cytotoxic but also compose a signaling network in the redox system. The formation, actions, key molecular interactions, and physiological and pathological relevance of redox signals in ECs remain unclear. We review the identities, sources, and biological actions of oxidants and reductants produced during EC function or dysfunction. Further, we discuss how ECs shape key redox sensors and examine the biological functions, transcriptional responses, and post-translational modifications evoked by the redox system in ECs. We summarize recent findings regarding the mechanisms by which redox signals regulate the fate of ECs and address the outcome of altered EC fate in health and disease. Future studies will examine if the redox biology of ECs can be targeted in pathophysiological conditions.

Keywords

Redox homeostasis Endothelial cell fate Atherosclerosis Hypertension Cancer Obesity Diabetes 

Abbreviations

3-MST

3-Mercaptopyruvate sulfurtransferase

AICAR

5-Amino-4-imidazole carboxamide riboside

AMPK

Adenosine monophosphate-activated protein kinase

BAT

Brown adipose tissue

BH4

Tetrahydrobiopterin

BMP

Bone morphogenetic protein

CAT

Catalase

CBS

Cystathionine β-synthase

CEP

ω-(2-Carboxyethyl)pyrrole

CSE

Cystathionine γ-lyase

EPA

Eicosapentaenoic acid

ER

Endoplasmic reticulum

ETC

Mitochondrial electron-transport chain

FoxO

Forkhead homeobox type O

Gpx

Glutathione peroxidase

GR

Glutathione reductase

Grx

Glutaredoxin

GTPCH I

GTP-cyclohydrolase I

H2O2

Hydrogen peroxide

HIF-1

Hypoxia-inducible factor 1

HUVEC

Human umbilical vein endothelial cells

ICAM-1

Intercellular adhesion molecule-1

IKK

IкB kinase

JNK

c-Jun N-terminal kinase

Keap1

Kelch-like ECH-associated protein 1

LDLR

Low-density lipoprotein receptor

LKB1

Liver kinase B1

MCP

Monocyte chemoattractant protein

NaHS

Sodium hydrosulfide

NO

Nitric oxide

NO2-FAs

Nitro-fatty acids

NOS

Nitric oxide synthase

NOX

NADPH oxidase

Nrf2

Nuclear factor erythroid-2-related factor 2

O2·−

Superoxide anion

OGD

Hypoxia and glucose deprivation

PAG

DL-propargylglycine

PI3K

Phosphoinositide 3-kinase

Prx

Peroxiredoxins

PTEN

Phosphatase and tensin homolog

RNS

Reactive nitrogen species

ROS

Reactive oxygen species

RSH

Thiol

RSO2H

Sulfinic acids

RSO3H

Sulfonic acids

RSOH

Sulfenic acids

RS-SG

S-glutathionylation

RS-SR, RS-SR’

Disulfide bonds

SIRT1

Sirtuin 1

SOD

Superoxide dismutase

SM

Smooth muscle

SREBP2

Sterol regulatory element binding protein 2

TP

Thromboxane receptor

Trx

Thioredoxin

VEGF

Vascular endothelial growth factor

VEGFR

VEGF receptor

VCAM-1

Vascular cell adhesion molecule-1

WAT

White adipose tissue

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Copyright information

© Springer Basel 2014

Authors and Affiliations

  1. 1.Section of Molecular Medicine, Department of Internal MedicineUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  2. 2.Department of Biochemistry and Molecular BiologyUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA

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