Date: Sunday, June 2, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: This study aims to discover new molecular mechanisms involved in and to develop new treatment for preventing ischemia reperfusion injury in heart transplantation.
*Methods: The effect of Erk-ELK1-miR-711 signalling on cardiac ischemia reperfusion (I/R) Injury was investigated in both an in vitro cell culture system and an in vivo murine heart transplantation model. Heart cells (H9c2) and donor hearts were treated with ERK inhibitor U0126 prior to or during 18 h cold ischemia, cell apoptosis/death, heart function, histopathological change and gene/miRNA expression were measured to assess the effect of effect of Erk-ELK1-miR-711 signalling on I/R injury.
*Results: 18 h cold I/R activated ERK-ELK1-miR-711 signaling and caused I/R injury. Pre-treatment with ERK inhibitor U0126 in vitro reduced ROS production, mitochondrial damage and apoptosis/death of H9 c2 cells, and expression of phosphorylated ERK1/2, ELK-1 and miR-711. Preserving donor hearts with UW solution containing U0126 improved heart graft function measured by ultrasound scanning, reduced apoptosis by TUNEL, fibrosis by Trachoma staining and neutrophil infiltration by an MPO assay. Inactivation of ERK-ELK1 by U0126 prevented ELK-1 binding to miR-711 promoter, leading to a reduction in miR-711 expression, therefore, inhibiting cell death and fibrosis.
*Conclusions: Activation of Erk-ELK1-miR-711 signalling induces cardiac I/R injury. Inhibition of this signalling can protect heart grafts from ischemia reperfusion injury in heart transplantation.
To cite this abstract in AMA style:Zheng H, Su Y, Zhu C, Veramkovich V, Zheng X. Erk-elk1-mir-711 Signalling In Cardiac Ischemia Reperfusion Injury In Heart Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/erk-elk1-mir-711-signalling-in-cardiac-ischemia-reperfusion-injury-in-heart-transplantation/. Accessed May 9, 2021.
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