Mr Wayne Sheedy W.Sheedy@hull.ac.uk
Research Group Manager
Sir Jules Thorn PhD Scholarship Programme 2016
People Involved
Professor Simon Hart S.Hart@hull.ac.uk
Professor in Respiratory Medicine
Project Description
Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the lungs that affects about 15,000 people in the UK. There is no curative treatment and 5-year survival in IPF is worse than many cancers. Despite this, the pathogenesis of IPF remains poorly understood. Improving future treatment options will depend on dissecting the mechanisms that trigger and perpetuate fibrosis in the lung.
Several lines of evidence point to a connection between blood platelets and pulmonary fibrosis. It is well known that platelets are critical for blood clotting, but activation of platelets also contributes to tissue inflammation through the secretion of vasoactive mediators and cytokines and by acting as anchors for activated monocytes. Release of potent pro-fibrotic mediators including platelet derived growth factor (PDGF) and transforming growth factor-beta (TGF-β) from platelets is of particular relevance given the established roles of these cytokines in animal models of IPF. Furthermore, lung sequestration of activated platelets correlates with increased collagen deposition in the bleomycin mouse model of pulmonary fibrosis. In humans, epidemiological studies have demonstrated strong associations between IPF and thrombotic vascular events including cardiovascular disease and venous thromboembolism. We hypothesise that a trigger for development of IPF is platelet activation in the lungs, adhesion to the pulmonary vascular endothelium, and release pro-inflammatory and pro-fibrotic cytokines.
Our studies of platelets challenged by physiological agonists have demonstrated an increased propensity for platelet activation in IPF. Using a plasma swap approach, we demonstrated that increased platelet activation is transferrable to normal platelets by incubating them in plasma from patients with IPF. The experiments proposed in this project have potential therapeutic implications. Restoring normal platelet responses to inhibition, if found deficient, or blocking excessive activation could be targets for future clinical trials, particularly given the recent availability of several novel antiplatelet and anticoagulant drugs.
Type of Project | Project |
---|---|
Status | Project Complete |
Funder(s) | Jules Thorn Charity |
Value | £83,999.00 |
Project Dates | Sep 1, 2016 - Aug 31, 2019 |
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