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TRPA1 as Target in Myocardial Infarction

Transient receptor potential cation channel subfamily A member 1 (TRPA1), an ion channel primarily expressed on sensory neurons, can be activated by substances occurring during myocardial infarction. Aims were to investigate whether activation, inhibition, or absence of TRPA1 affects infarcts and to...

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Autores principales: Hoebart, Clara, Kiss, Attila, Pilz, Patrick M., Szabo, Petra L., Podesser, Bruno K., Fischer, Michael J. M., Heber, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917254/
https://www.ncbi.nlm.nih.gov/pubmed/36768836
http://dx.doi.org/10.3390/ijms24032516
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author Hoebart, Clara
Kiss, Attila
Pilz, Patrick M.
Szabo, Petra L.
Podesser, Bruno K.
Fischer, Michael J. M.
Heber, Stefan
author_facet Hoebart, Clara
Kiss, Attila
Pilz, Patrick M.
Szabo, Petra L.
Podesser, Bruno K.
Fischer, Michael J. M.
Heber, Stefan
author_sort Hoebart, Clara
collection PubMed
description Transient receptor potential cation channel subfamily A member 1 (TRPA1), an ion channel primarily expressed on sensory neurons, can be activated by substances occurring during myocardial infarction. Aims were to investigate whether activation, inhibition, or absence of TRPA1 affects infarcts and to explore underlying mechanisms. In the context of myocardial infarction, rats received a TRPA1 agonist, an antagonist, or vehicle at different time points, and infarct size was assessed. Wild type and TRPA1 knockout mice were also compared in this regard. In vitro, sensory neurons were co-cultured with cardiomyocytes and subjected to a model of ischemia-reperfusion. Although there was a difference between TRPA1 activation or inhibition in vivo, no experimental group was different to control animals in infarct size, which also applies to animals lacking TRPA1. In vitro, survival probability of cardiomyocytes challenged by ischemia-reperfusion increased from 32.8% in absence to 45.1% in presence of sensory neurons, which depends, at least partly, on TRPA1. This study raises doubts about whether TRPA1 is a promising target to reduce myocardial damage within a 24 h period. The results are incompatible with relevant enlargements of infarcts by TRPA1 activation or inhibition, which argues against adverse effects when TRPA1 is targeted for other indications.
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spelling pubmed-99172542023-02-11 TRPA1 as Target in Myocardial Infarction Hoebart, Clara Kiss, Attila Pilz, Patrick M. Szabo, Petra L. Podesser, Bruno K. Fischer, Michael J. M. Heber, Stefan Int J Mol Sci Article Transient receptor potential cation channel subfamily A member 1 (TRPA1), an ion channel primarily expressed on sensory neurons, can be activated by substances occurring during myocardial infarction. Aims were to investigate whether activation, inhibition, or absence of TRPA1 affects infarcts and to explore underlying mechanisms. In the context of myocardial infarction, rats received a TRPA1 agonist, an antagonist, or vehicle at different time points, and infarct size was assessed. Wild type and TRPA1 knockout mice were also compared in this regard. In vitro, sensory neurons were co-cultured with cardiomyocytes and subjected to a model of ischemia-reperfusion. Although there was a difference between TRPA1 activation or inhibition in vivo, no experimental group was different to control animals in infarct size, which also applies to animals lacking TRPA1. In vitro, survival probability of cardiomyocytes challenged by ischemia-reperfusion increased from 32.8% in absence to 45.1% in presence of sensory neurons, which depends, at least partly, on TRPA1. This study raises doubts about whether TRPA1 is a promising target to reduce myocardial damage within a 24 h period. The results are incompatible with relevant enlargements of infarcts by TRPA1 activation or inhibition, which argues against adverse effects when TRPA1 is targeted for other indications. MDPI 2023-01-28 /pmc/articles/PMC9917254/ /pubmed/36768836 http://dx.doi.org/10.3390/ijms24032516 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hoebart, Clara
Kiss, Attila
Pilz, Patrick M.
Szabo, Petra L.
Podesser, Bruno K.
Fischer, Michael J. M.
Heber, Stefan
TRPA1 as Target in Myocardial Infarction
title TRPA1 as Target in Myocardial Infarction
title_full TRPA1 as Target in Myocardial Infarction
title_fullStr TRPA1 as Target in Myocardial Infarction
title_full_unstemmed TRPA1 as Target in Myocardial Infarction
title_short TRPA1 as Target in Myocardial Infarction
title_sort trpa1 as target in myocardial infarction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917254/
https://www.ncbi.nlm.nih.gov/pubmed/36768836
http://dx.doi.org/10.3390/ijms24032516
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