Artículo
Chemical chaperones improve the functional recovery of stunned myocardium by attenuating the endoplasmic reticulum stress
Mariángelo, Juan Ignacio Elio
; Roman, Barbara Soledad
; Silvestri, María Agustina; Salas, Margarita Ana; Vittone, Leticia Beatriz
; Said, Maria Matilde
; Mundiña, Cecilia Beatriz
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Fecha de publicación:
05/08/2019
Editorial:
Wiley Blackwell Publishing, Inc
Revista:
Acta Physiologica
ISSN:
1748-1708
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Aim: Myocardial ischaemia/reperfusion (I/R) produces structural and functional alterations depending on the duration of ischaemia. Brief ischaemia followed by reperfusion causes reversible contractile dysfunction (stunned heart) but long-lasting ischaemia 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-ischaemic cardiac performance of the stunned heart. Methods: Perfused rat hearts were subjected to 20 minutes of ischaemia followed by 30 minutes of reperfusion. UPR markers were evaluated by qRT-PCR and western blot. Post-ischaemic mechanical recovery was measured in absence and presence of two chemical chaperones: tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyric acid (4-PBA). Results: Analysis of mRNA and protein levels of various ER stress effectors demonstrated that different UPR signalling cascades, involving both pro-survival and pro-apoptotic pathways, are activated. Inhibition of the UPR with chemical chaperones improved the post-ischaemic recovery of cardiac mechanical function without affecting the I/R-induced increase in oxidative stress. Conclusion: 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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Articulos(CIC)
Articulos de CENTRO DE INVEST.CARDIOVASCULARES (I)
Articulos de CENTRO DE INVEST.CARDIOVASCULARES (I)
Citación
Mariángelo, Juan Ignacio Elio; Roman, Barbara Soledad; Silvestri, María Agustina; Salas, Margarita Ana; Vittone, Leticia Beatriz; et al.; Chemical chaperones improve the functional recovery of stunned myocardium by attenuating the endoplasmic reticulum stress; Wiley Blackwell Publishing, Inc; Acta Physiologica; 228; 2; 5-8-2019; 1-20
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