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Plasma proteomics reveals gestational age-specific responses to mechanical ventilation and identifies the mechanistic pathways that initiate preterm lung injury

Citation

Pereira-Fantini, PM and Byars, SG and McCall, KE and Perkins, EJ and Oakley, RB and Dellaca, RL and Dargaville, PA and Davis, PG and Ignjatovic, V and Tingay, DG, Plasma proteomics reveals gestational age-specific responses to mechanical ventilation and identifies the mechanistic pathways that initiate preterm lung injury, Scientific Reports, 8, (1) Article 12616. ISSN 2045-2322 (2018) [Refereed Article]


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Copyright 2018 the authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.1038/s41598-018-30868-x

Abstract

The preterm lung is particularly vulnerable to ventilator-induced lung injury (VILI) as a result of mechanical ventilation. However the developmental and pathological cellular mechanisms influencing the changing patterns of VILI have not been comprehensively delineated, preventing the advancement of targeted lung protective therapies. This study aimed to use SWATH-MS to comprehensively map the plasma proteome alterations associated with the initiation of VILI following 60 minutes of standardized mechanical ventilation from birth in three distinctly different developmental lung states; the extremely preterm, preterm and term lung using the ventilated lamb model. Across these gestations, 34 proteins were differentially altered in matched plasma samples taken at birth and 60 minutes. Multivariate analysis of the plasma proteomes confirmed a gestation-specific response to mechanical ventilation with 79% of differentially-expressed proteins altered in a single gestation group only. Six cellular and molecular functions and two physiological functions were uniquely enriched in either the extremely preterm or preterm group. Correlation analysis supported gestation-specific protein-function associations within each group. In identifying the gestation-specific proteome and functional responses to ventilation we provide the founding evidence required for the potential development of individualized respiratory support approaches tailored to both the developmental and pathological state of the lung.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Paediatrics and Reproductive Medicine
Research Field:Paediatrics
Objective Division:Health
Objective Group:Specific Population Health (excl. Indigenous Health)
Objective Field:Child Health
Author:Dargaville, PA (Professor Peter Dargaville)
ID Code:128139
Year Published:2018
Deposited By:Menzies Institute for Medical Research
Deposited On:2018-09-05
Last Modified:2018-10-08
Downloads:4 View Download Statistics

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