Chemical chaperones improve the functional recovery of stunned myocardium by attenuating the endoplasmic reticulum stress

<b>Aim</b>: Myocardial ischemia/reperfusion (I/R) produces structural and functional alterations depending on the duration of ischemia. Brief ischemia followed by reperfusion causes reversible contractile dysfunction (stunned heart) but long -lasting ischemia followed by reperfusion can...

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Autores principales: Mariángelo, Juan Ignacio Elio, Román, Bárbara Soledad, Silvestri, María Agustina, Salas, Margarita Ana, Vittone, Leticia Beatriz, Said, María Matilde, Mundiña-Weilenmann, Cecilia
Formato: Articulo Preprint
Lenguaje:Inglés
Publicado: 2019
Materias:
Ciencias Médicas
Medicina
Myocardial ischemia/reperfusion
Endoplasmic reticulum stress
Chemical chaperones
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/127368
https://onlinelibrary.wiley.com/doi/10.1111/apha.13358
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-127368
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Medicina
Myocardial ischemia/reperfusion
Endoplasmic reticulum stress
Chemical chaperones
spellingShingle Ciencias Médicas
Medicina
Myocardial ischemia/reperfusion
Endoplasmic reticulum stress
Chemical chaperones
Mariángelo, Juan Ignacio Elio
Román, Bárbara Soledad
Silvestri, María Agustina
Salas, Margarita Ana
Vittone, Leticia Beatriz
Said, María Matilde
Mundiña-Weilenmann, Cecilia
Chemical chaperones improve the functional recovery of stunned myocardium by attenuating the endoplasmic reticulum stress
topic_facet Ciencias Médicas
Medicina
Myocardial ischemia/reperfusion
Endoplasmic reticulum stress
Chemical chaperones
description <b>Aim</b>: Myocardial ischemia/reperfusion (I/R) produces structural and functional alterations depending on the duration of ischemia. Brief ischemia followed by reperfusion causes reversible contractile dysfunction (stunned heart) but long -lasting ischemia followed by reperfusion can result in irreversible injury with cell death. Events during I/R can alter endoplasmic reticulum (ER) function leading to the accumulation of unfolded/misfolded proteins. The resulting ER stress induces activation of several signal transduction pathways, known as unfolded protein response (UPR). Experimental evidence shows that UPR contributes to cell death in irreversible I/R injury, however there is still uncertainty for its occurrence in the stunned myocardium . This study investigated the ER stress response and its functional impact on the post -ischemic cardiac performance of the stunned heart. <b>Methods</b>: Perfused rat hearts were subjected to 20 min of ischemia followed by 30 min of reperfusion . UPR markers were evaluated by qRT -PCR and Western blot. Post -ischemic mechanical recovery was measured in absence and presence of two chemical chaperones: tauroursodeoxycholic acid (TUDCA) and 4 -phenylbutyric acid (4 -PBA). <b>Results</b>: Analysis of mRNA and protein levels of various ER stress effectors demonstrated that different UPR signaling cascades, involving both pro -survival and pro -apoptotic pathways, are activated. Inhibition of the UPR with chemical chaperones improved the post -ischemic recovery of cardiac mechanical function without affecting the I/R -induced increase in oxidative stress. <b>Conclusion</b>: Our results suggest that prevention of ER stress by chemical chaperones could be a therapeutic tool to limit deterioration of the contractile function in clinical settings in which the phenomenon of myocardial stunning is present.
format Articulo
Preprint
author Mariángelo, Juan Ignacio Elio
Román, Bárbara Soledad
Silvestri, María Agustina
Salas, Margarita Ana
Vittone, Leticia Beatriz
Said, María Matilde
Mundiña-Weilenmann, Cecilia
author_facet Mariángelo, Juan Ignacio Elio
Román, Bárbara Soledad
Silvestri, María Agustina
Salas, Margarita Ana
Vittone, Leticia Beatriz
Said, María Matilde
Mundiña-Weilenmann, Cecilia
author_sort Mariángelo, Juan Ignacio Elio
title Chemical chaperones improve the functional recovery of stunned myocardium by attenuating the endoplasmic reticulum stress
title_short Chemical chaperones improve the functional recovery of stunned myocardium by attenuating the endoplasmic reticulum stress
title_full Chemical chaperones improve the functional recovery of stunned myocardium by attenuating the endoplasmic reticulum stress
title_fullStr Chemical chaperones improve the functional recovery of stunned myocardium by attenuating the endoplasmic reticulum stress
title_full_unstemmed Chemical chaperones improve the functional recovery of stunned myocardium by attenuating the endoplasmic reticulum stress
title_sort chemical chaperones improve the functional recovery of stunned myocardium by attenuating the endoplasmic reticulum stress
publishDate 2019
url http://sedici.unlp.edu.ar/handle/10915/127368
https://onlinelibrary.wiley.com/doi/10.1111/apha.13358
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