Circulating miRNAs as Promising Biomarkers to Evaluate ECMO Treatment Responses in ARDS Patients

Gennaro Martucci,Giovanna Occhipinti,Giovanna Panarello,Vitale Miceli,Antonio Arcadipane,Claudia Carcione,Fabio Tuzzolino,Alessandro Bertani,Pier Giulio Conaldi

doi:10.3390/membranes11080551

Abstract

The use of extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) has increased in the last decade. However, mortality remains high, and the complexity of ECMO requires individualized treatment. There are some biomarkers to monitor progression and predict clinical outcomes of ARDS. This project aims to advance the management of ARDS patients treated with ECMO by exploring miRNA expression in whole blood. The analysis was conducted on two groups with different length of ECMO: Group A (longer runs) and group B (shorter runs). We analyzed miRNAs before ECMO cannulation, and at 7 and 14 days of ECMO support. Our results showed that in the group B patients, 11 deregulated miRNAs were identified, and showed an opposite trend of expression compared to the group A patients. In silico analysis revealed that these 11 miRNAs were related to processes involved in the pathogenesis and evolution of ARDS. This scenario could represent homeostatic mechanisms by which, in ECMO responsive patients, pathways activated during ARDS progression are switched-off. Circulating miRNAs could represent promising biomarkers to monitor the evolution of ARDS under ECMO support. Further studies may shed light on this topic to improve a personalized approach in such a complex setting of patients.

Highlights

The use of veno-venous extracorporeal membrane oxygenation (ECMO) is an established tool in the most severe cases of patients with acute respiratory distress syndrome (ARDS)
With miRNET we investigated the functional implications of miRNA deregulation in ECMO-treated ARDS patients and generated a protein–protein interaction network of proteins targeted by deregulated miRNAs and involved in crucial pathways of ARDS pathogenesis
We collected blood samples from ten consecutive ARDS patients supported by ECMO

Summary

Introduction

The use of veno-venous extracorporeal membrane oxygenation (ECMO) is an established tool in the most severe cases of patients with acute respiratory distress syndrome (ARDS). ECMO provides a temporary circulatory support that can substitute the lung function for days to months if mechanical ventilation (MV) cannot adequately guarantee gas exchanges or the risk of ventilator-induced lung injury is too high. In a wide clinical view, ECMO aims at allowing the “lung rest” by lowering airway pressures and tidal volumes. Despite numerous advances in ECMO treatment, the mortality rate of patients remains unacceptably high [1,2]. The mortality rates are very variable [2,6,7,8], and it has been highlighted that an appropriate patient selection and experience in ECMO management are the keys for successful treatment [9]

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Methods

Results