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

Acta Physiologica
Juan Ignacio Elio MariángeloCecilia Mundiña-Weilenmann

Abstract

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. 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). Analysis of mRNA and protein levels ...Continue Reading

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Citations

Jun 1, 2021·Oxidative Medicine and Cellular Longevity·Mi XiangXiangning Cui
Aug 22, 2021·Acta Physiologica·Karin M Kirschner

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