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The pulmonary endothelium in acute respiratory distress syndrome: insights and therapeutic opportunities
  1. Fraser R Millar1,
  2. Charlotte Summers2,3,
  3. Mark J Griffiths1,4,
  4. Mark R Toshner3,
  5. Alastair G Proudfoot1,5
  1. 1Leukocyte Biology Section, National Heart & Lung Institute, Imperial College, London, UK
  2. 2Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK
  3. 3Papworth Hospital NHS Foundation Trust, Cambridge, UK
  4. 4NIHR Respiratory Biomedical Research Unit, Royal Brompton & Harefield Hospital, NHS Foundation Trust, London, UK
  5. 5Frederick Meijer Heart & Vascular Institute, Spectrum Health, Grand Rapids, Michigan, USA
  1. Correspondence to Dr Alastair Proudfoot, Frederick Meijer Heart & Vascular Institute, Spectrum Health, 100 Michigan Street NE, Grand Rapids, MI 49503, USA; Alastair.Proudfoot{at}spectrumhealth.org

Abstract

The pulmonary endothelium is a dynamic, metabolically active layer of squamous endothelial cells ideally placed to mediate key processes involved in lung homoeostasis. Many of these are disrupted in acute respiratory distress syndrome (ARDS), a syndrome with appreciable mortality and no effective pharmacotherapy. In this review, we consider the role of the pulmonary endothelium as a key modulator and orchestrator of ARDS, highlighting advances in our understanding of endothelial pathobiology and their implications for the development of endothelial-targeted therapeutics including cell-based therapies. We also discuss mechanisms to facilitate the translation of preclinical data into effective therapies including the application of biomarkers to phenotype patients with ARDS with a predominance of endothelial injury and emerging biotechnologies that could enhance delivery, discovery and testing of lung endothelial-specific therapeutics.

  • ARDS
  • Neutrophil Biology
  • Pulmonary oedema

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