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Redox regulation of endothelial cell fate

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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.

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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

O ·−2 :

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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Acknowledgments

The authors sincerely apologize to those colleagues whose original work was not cited due to limited space. The authors also thank all current and former members of Dr. Zou’s laboratory for the work described in this review. This study was supported by funding from the following agencies: National Institutes of Health RO1 (HL110488, HL105157, HL096032, HL089920, HL080499, HL079584, and HL074399), the Warren Chair in Diabetes Research of the University of Oklahoma Health Sciences Center (all to Dr. Zou), Scientist Development Grant (11SDG5560036) from National Center of American Heart Association, and Oklahoma Center for the Advancement of Science and Technology (HR12-061) (both to Dr. Song). Dr. Zou is a recipient of the National Established Investigator Award of the American Heart Association.

Conflict of interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Section of Molecular Medicine, Department of Internal Medicine, University of Oklahoma Health Sciences Center, 941 Stanton L Young Blvd., Oklahoma City, OK, 73104, USA

    Ping Song & Ming-Hui Zou

  2. Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    Ming-Hui Zou

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  1. Ping Song
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  2. Ming-Hui Zou
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Correspondence to Ping Song or Ming-Hui Zou.

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Song, P., Zou, MH. Redox regulation of endothelial cell fate. Cell. Mol. Life Sci. 71, 3219–3239 (2014). https://doi.org/10.1007/s00018-014-1598-z

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  • DOI: https://doi.org/10.1007/s00018-014-1598-z

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