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: | , , , , , , |
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| Formato: | Articulo Preprint |
| Lenguaje: | Inglés |
| Publicado: |
2019
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| Materias: | |
| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/127368 https://onlinelibrary.wiley.com/doi/10.1111/apha.13358 |
| Aporte de: |
| Sumario: | <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. |
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