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

Cell Mol Life Sci. 2019 Oct;76(20):3969-3985. doi: 10.1007/s00018-019-03195-1. Epub 2019 Jun 19.

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.

Keywords: Biomarkers; Cardiovascular diseases; Endoplasmic reticulum; Selenoprotein T; Selenoproteins.

Publication types

  • Review

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Cardiotonic Agents / therapeutic use*
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / pathology
  • Cardiovascular Diseases / therapy
  • Endoplasmic Reticulum Stress / drug effects*
  • Gene Expression Regulation
  • Glutathione Peroxidase / metabolism
  • Humans
  • Molecular Targeted Therapy / methods
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Oxidative Stress / drug effects
  • Peptides / therapeutic use*
  • Protein Isoforms / agonists
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Selenocysteine / metabolism*
  • Selenoproteins / agonists
  • Selenoproteins / genetics*
  • Selenoproteins / metabolism
  • Thioredoxin-Disulfide Reductase / metabolism

Substances

  • Antioxidants
  • Cardiotonic Agents
  • Peptides
  • Protein Isoforms
  • Reactive Oxygen Species
  • SELENOT protein, human
  • Selenoproteins
  • Selenocysteine
  • Glutathione Peroxidase
  • Thioredoxin-Disulfide Reductase