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Progress in the emerging role of selenoproteins in cardiovascular disease: focus on endoplasmic reticulum-resident selenoproteins

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Abstract

Cardiovascular diseases represent one of the most important health problems of developed countries. One of the main actors involved in the onset and development of cardiovascular diseases is the increased production of reactive oxygen species that, through lipid peroxidation, protein oxidation and DNA damage, induce oxidative stress and cell death. Basic and clinical research are ongoing to better understand the endogenous antioxidant mechanisms that counteract oxidative stress, which may allow to identify a possible therapeutic targeting/application in the field of stress-dependent cardiovascular pathologies. In this context, increasing attention is paid to the glutathione/glutathione-peroxidase and to the thioredoxin/thioredoxin-reductase systems, among the most potent endogenous antioxidative systems. These key enzymes, belonging to the selenoprotein family, have a well-established function in the regulation of the oxidative cell balance. The aim of the present review was to highlight the role of selenoproteins in cardiovascular diseases, introducing the emerging cardioprotective role of endoplasmic reticulum-resident members and in particular one of them, namely selenoprotein T or SELENOT. Accumulating evidence indicates that the dysfunction of different selenoproteins is involved in the susceptibility to oxidative stress and its associated cardiovascular alterations, such as congestive heart failure, coronary diseases, impaired cardiac structure and function. Some of them are under investigation as useful pathological biomarkers. In addition, SELENOT exhibited intriguing cardioprotective effects by reducing the cardiac ischemic damage, in terms of infarct size and performance. In conclusion, selenoproteins could represent valuable targets to treat and diagnose cardiovascular diseases secondary to oxidative stress, opening a new avenue in the field of related therapeutic strategies.

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Abbreviations

CVDs:

Cardiovascular diseases

Cys:

Cysteine

DIO:

Iodothyronine deiodinases

ER:

Endoplasmic reticulum

ERAD:

ER-associated protein degradation

FGD:

Familial glucocorticoid deficiency

GPX:

Glutathione peroxidase

H2O2 :

Hydrogen peroxide

HbA1c:

Glycated hemoglobin

HF:

Heart failure

HNO:

Azanone

I/R:

Ischemia/reperfusion

IL-1β:

Interleukin-1β

IL-6:

Interleukin-6

Met:

Methionine

MI:

Myocardial infarction

MSRB1:

Methionine sulfoxide reductase B1

NO:

Nitric oxide

O ·2 :

Superoxide radical

OH· :

Hydroxyl radical

ONOO-:

Peroxynitrite

PACAP:

Pituitary adenylate cyclase-activating peptide

PCH2D:

Ponto-cerebellar hypoplasia type 2D

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

RSNO:

S-Nitrosothiols

S:

Sulfur

Se:

Selenium

Sec:

Selenocysteine

SECISBP2:

SECIS binding protein 2

SELENOH:

Selenoprotein H

SELENOI:

Selenoprotein I

SELENOK:

Selenoprotein K

SELENOM:

Selenoprotein M

SELENON:

Selenoprotein N

SELENOO:

Selenoprotein O

SELENOP:

Selenoprotein P

SELENOS:

Selenoprotein S

SELENOT:

Selenoprotein T

SELENOV:

Selenoprotein V

SELENOW:

Selenoprotein W

SELENOF:

Selenoprotein F

SEPHS2:

Selenophosphate synthetase 2

SEPSECS:

Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase

SNPs:

Single nucleotide polymorphisms

STEMI:

ST-segment elevation MI

TNF-α:

Tumor necrosis factor-α

TRU-TCA1-1:

Transfer RNA-Sec [TCA] 1-1

Trx:

Thioredoxin

TXNRD:

Thioredoxin reductase

UPR:

Unfolded protein response

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Acknowledgements

This work has been partially supported by “Fondazione Umberto Veronesi” Post-Doctoral Fellowship (2019) to TP and by Doctorate School in Life Science, University of Calabria.

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  1. Laboratory of Cellular and Molecular Cardiovascular Patho-physiology, Department of Biology, E. and E.S., University of Calabria, Rende, Italy

    Carmine Rocca, Teresa Pasqua & Tommaso Angelone

  2. UNIROUEN, Inserm U1239, Neuronal and Neuroendocrine Differentiation and Communication Laboratory, Rouen-Normandie University, 76821, Mont-Saint-Aignan, France

    Carmine Rocca, Loubna Boukhzar & Youssef Anouar

  3. Institute for Research and Innovation in Biomedicine, 76000, Rouen, France

    Carmine Rocca, Loubna Boukhzar & Youssef Anouar

  4. “Fondazione Umberto Veronesi”, Milan, Italy

    Teresa Pasqua

  5. National Institute of Cardiovascular Research (INRC), Bologna, Italy

    Tommaso Angelone

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  1. Carmine Rocca
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Rocca, C., Pasqua, T., Boukhzar, L. et al. Progress in the emerging role of selenoproteins in cardiovascular disease: focus on endoplasmic reticulum-resident selenoproteins. Cell. Mol. Life Sci. 76, 3969–3985 (2019). https://doi.org/10.1007/s00018-019-03195-1

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