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The Role of Glucocorticoid Receptor and Oxytocin Receptor in the Septic Heart in a Clinically Relevant, Resuscitated Porcine Model With Underlying Atherosclerosis

The pathophysiology of sepsis-induced myocardial dysfunction is not resolved to date and comprises inflammation, barrier dysfunction and oxidative stress. Disease-associated reduction of tissue cystathionine-γ-lyase (CSE) expression, an endogenous H(2)S-producing enzyme, is associated with oxidative...

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Autores principales: Merz, Tamara, Denoix, Nicole, Wigger, Daniela, Waller, Christiane, Wepler, Martin, Vettorazzi, Sabine, Tuckermann, Jan, Radermacher, Peter, McCook, Oscar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239997/
https://www.ncbi.nlm.nih.gov/pubmed/32477273
http://dx.doi.org/10.3389/fendo.2020.00299
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author Merz, Tamara
Denoix, Nicole
Wigger, Daniela
Waller, Christiane
Wepler, Martin
Vettorazzi, Sabine
Tuckermann, Jan
Radermacher, Peter
McCook, Oscar
author_facet Merz, Tamara
Denoix, Nicole
Wigger, Daniela
Waller, Christiane
Wepler, Martin
Vettorazzi, Sabine
Tuckermann, Jan
Radermacher, Peter
McCook, Oscar
author_sort Merz, Tamara
collection PubMed
description The pathophysiology of sepsis-induced myocardial dysfunction is not resolved to date and comprises inflammation, barrier dysfunction and oxidative stress. Disease-associated reduction of tissue cystathionine-γ-lyase (CSE) expression, an endogenous H(2)S-producing enzyme, is associated with oxidative stress, barrier dysfunction and organ injury. CSE-mediated cardio-protection has been suggested to be related the upregulation of oxytocin receptor (OTR). CSE can also mediate glucocorticoid receptor (GR) signaling, which is important for normal heart function. A sepsis-related loss of cardiac CSE expression associated with impaired organ function has been reported previously. The aim of this current post hoc study was to investigate the role of cardiac GR and OTR after polymicrobial sepsis in a clinically relevant, resuscitated, atherosclerotic porcine model. Anesthetized and instrumented FBM (Familial Hypercholesterolemia Bretoncelles Meishan) pigs with high fat diet-induced atherosclerosis underwent poly-microbial septic shock (n = 8) or sham procedure (n = 5), and subsequently received intensive care therapy with fluid and noradrenaline administration for 24 h. Cardiac protein expression and mRNA levels were analyzed. Systemic troponin, a marker of cardiac injury, was significantly increased in septic animals in contrast to sham, whereas OTR and GR expression in septic hearts were reduced, along with a down-regulation of anti-inflammatory GR target genes and the antioxidant transcription factor NRF2. These results suggest a potential interplay between GR, CSE, and OTR in sepsis-mediated oxidative stress, inflammation and cardiac dysfunction.
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spelling pubmed-72399972020-05-29 The Role of Glucocorticoid Receptor and Oxytocin Receptor in the Septic Heart in a Clinically Relevant, Resuscitated Porcine Model With Underlying Atherosclerosis Merz, Tamara Denoix, Nicole Wigger, Daniela Waller, Christiane Wepler, Martin Vettorazzi, Sabine Tuckermann, Jan Radermacher, Peter McCook, Oscar Front Endocrinol (Lausanne) Endocrinology The pathophysiology of sepsis-induced myocardial dysfunction is not resolved to date and comprises inflammation, barrier dysfunction and oxidative stress. Disease-associated reduction of tissue cystathionine-γ-lyase (CSE) expression, an endogenous H(2)S-producing enzyme, is associated with oxidative stress, barrier dysfunction and organ injury. CSE-mediated cardio-protection has been suggested to be related the upregulation of oxytocin receptor (OTR). CSE can also mediate glucocorticoid receptor (GR) signaling, which is important for normal heart function. A sepsis-related loss of cardiac CSE expression associated with impaired organ function has been reported previously. The aim of this current post hoc study was to investigate the role of cardiac GR and OTR after polymicrobial sepsis in a clinically relevant, resuscitated, atherosclerotic porcine model. Anesthetized and instrumented FBM (Familial Hypercholesterolemia Bretoncelles Meishan) pigs with high fat diet-induced atherosclerosis underwent poly-microbial septic shock (n = 8) or sham procedure (n = 5), and subsequently received intensive care therapy with fluid and noradrenaline administration for 24 h. Cardiac protein expression and mRNA levels were analyzed. Systemic troponin, a marker of cardiac injury, was significantly increased in septic animals in contrast to sham, whereas OTR and GR expression in septic hearts were reduced, along with a down-regulation of anti-inflammatory GR target genes and the antioxidant transcription factor NRF2. These results suggest a potential interplay between GR, CSE, and OTR in sepsis-mediated oxidative stress, inflammation and cardiac dysfunction. Frontiers Media S.A. 2020-05-14 /pmc/articles/PMC7239997/ /pubmed/32477273 http://dx.doi.org/10.3389/fendo.2020.00299 Text en Copyright © 2020 Merz, Denoix, Wigger, Waller, Wepler, Vettorazzi, Tuckermann, Radermacher and McCook. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Merz, Tamara
Denoix, Nicole
Wigger, Daniela
Waller, Christiane
Wepler, Martin
Vettorazzi, Sabine
Tuckermann, Jan
Radermacher, Peter
McCook, Oscar
The Role of Glucocorticoid Receptor and Oxytocin Receptor in the Septic Heart in a Clinically Relevant, Resuscitated Porcine Model With Underlying Atherosclerosis
title The Role of Glucocorticoid Receptor and Oxytocin Receptor in the Septic Heart in a Clinically Relevant, Resuscitated Porcine Model With Underlying Atherosclerosis
title_full The Role of Glucocorticoid Receptor and Oxytocin Receptor in the Septic Heart in a Clinically Relevant, Resuscitated Porcine Model With Underlying Atherosclerosis
title_fullStr The Role of Glucocorticoid Receptor and Oxytocin Receptor in the Septic Heart in a Clinically Relevant, Resuscitated Porcine Model With Underlying Atherosclerosis
title_full_unstemmed The Role of Glucocorticoid Receptor and Oxytocin Receptor in the Septic Heart in a Clinically Relevant, Resuscitated Porcine Model With Underlying Atherosclerosis
title_short The Role of Glucocorticoid Receptor and Oxytocin Receptor in the Septic Heart in a Clinically Relevant, Resuscitated Porcine Model With Underlying Atherosclerosis
title_sort role of glucocorticoid receptor and oxytocin receptor in the septic heart in a clinically relevant, resuscitated porcine model with underlying atherosclerosis
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239997/
https://www.ncbi.nlm.nih.gov/pubmed/32477273
http://dx.doi.org/10.3389/fendo.2020.00299
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