Clarke, L.; (2009) Endothelial injury and repair in vasculitis of the young. Doctoral thesis , UCL (University College London).

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Abstract

The vasculitides are a wide spectrum of disorders which are characterised by vascular inflammation. Endothelial injury can occur as a consequence of inappropriate inflammation and is central to the pathogenesis of these varied diseases. This thesis documents the development of assays for detection of novel biomarkers of endothelial injury and/or activation and subsequent reparative responses in children with primary systemic vasculitis. It focuses in particular on circulating endothelial cells, cellular microparticles, growth factors involved in angiogenesis/vasculogenesis and endothelial progenitor cells. Circulating endothelial cells are mature endothelial cells which have become detached from the vessel wall and represent a highly damaged vasculature and were found to be significantly higher in children with active primary systemic vasculitis compared to healthy child controls and patients in remission. Microparticles are released from activated cells, including the endothelium and leukocytes. In this study endothelial and monocyte derived microparticles were found to be elevated during active vasculitis. Growth factors released in response to endothelial injury regulate reparative responses, of which endothelial progenitor cells may play a key role. In this study, patients at disease onset prior to treatment were found to have significantly higher levels of growth factors and endothelial progenitor cells, which decreased with remission inducing therapy. Overall this thesis has investigated the changes in these interlinked biomarkers of injury and repair during active disease, remission and disease flare.

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