title: The pulmonary endothelium in acute respiratory distress syndrome: insights and therapeutic opportunities.
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.
authors.affiliation: Leukocyte Biology Section, National Heart & Lung Institute, Imperial College, London, UK.
authors.forename: Fraser R
authors.initials: FR
authors.lastname: Millar
authors.affiliation: Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK Papworth Hospital NHS Foundation Trust, Cambridge, UK.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Summers
authors.affiliation: Leukocyte Biology Section, National Heart & Lung Institute, Imperial College, London, UK NIHR Respiratory Biomedical Research Unit, Royal Brompton & Harefield Hospital, NHS Foundation Trust, London, UK.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Griffiths
authors.affiliation: Papworth Hospital NHS Foundation Trust, Cambridge, UK.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Toshner
authors.affiliation: Leukocyte Biology Section, National Heart & Lung Institute, Imperial College, London, UK Frederick Meijer Heart & Vascular Institute, Spectrum Health, Grand Rapids, Michigan, USA.
authors.forename: Alastair G
authors.initials: AG
authors.lastname: Proudfoot
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D004727:Endothelium / Q000503:physiopathology*; D006439:Hemodynamics; D006706:Homeostasis; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008168:Lung / Q000503:physiopathology*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012128:Respiratory Distress Syndrome / Q000503:physiopathology* / Q000628:therapy*
chemical_list: D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors
keywords: ARDS; Neutrophil Biology; Pulmonary oedema