RIPK3 mediates pathogenesis of experimental ventilator-induced lung injury. Academic Article uri icon

Overview

abstract

  • In patients requiring ventilator support, mechanical ventilation (MV) may induce acute lung injury (ventilator-induced lung injury [VILI]). VILI is associated with substantial morbidity and mortality in mechanically ventilated patients with and without acute respiratory distress syndrome. At the cellular level, VILI induces necrotic cell death. However, the contribution of necroptosis, a programmed form of necrotic cell death regulated by receptor-interacting protein-3 kinase (RIPK3) and mixed-lineage kinase domain-like pseudokinase (MLKL), to the development of VILI remains unexplored. Here, we show that plasma levels of RIPK3, but not MLKL, were higher in patients with MV (i.e., those prone to VILI) than in patients without MV (i.e., those less likely to have VILI) in two large intensive care unit cohorts. In mice, RIPK3 deficiency, but not MLKL deficiency, ameliorated VILI. In both humans and mice, VILI was associated with impaired fatty acid oxidation (FAO), but in mice this association was not observed under conditions of RIPK3 deficiency. These findings suggest that FAO-dependent RIPK3 mediates pathogenesis of acute lung injury.

publication date

  • May 3, 2018

Research

keywords

  • Protein Kinases
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Respiration, Artificial
  • Ventilator-Induced Lung Injury

Identity

PubMed Central ID

  • PMC6012515

Scopus Document Identifier

  • 85058198220

Digital Object Identifier (DOI)

  • 10.1172/jci.insight.97102

PubMed ID

  • 29720570

Additional Document Info

volume

  • 3

issue

  • 9