The pulmonary endothelium in acute respiratory distress syndrome: insights and therapeutic opportunities.

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.This work was supported by the Royal Brompton and Harefield NHS Foundation Trust, NIHR Respiratory Biomedical Research Unit, London, United Kingdom COMPETING INTERESTS CS was a co-investigator on a project grant, funded GlaxoSmithKline, which undertook preclinical assessment of the effects of a potential ARDS therapy on human neutrophils (2012-14). MG & CS have received fees for consultancy from GSK. MG and AGP have had unrestricted Project Grant support from GlaxoSmithKline. FUNDING CS is a Wellcome Trust Postdoctoral Clinical Research Training Fellow. [WT101692MA].This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by the British Medical Journal