P2X7 receptors and renal vascular remodelling in hypertensive kidney disease

Hypertension promotes remodelling of renal arteries and arterioles. These structural and mechanical alterations are intimately linked with changes in endothelial cell function, vascular calcification and the onset of fibrosis. Extracellular ATP is widely recognised as a paracrine danger signal. ATP is released from injured and damaged cells to activate P2 receptors that orchestrate local inflammatory and remodelling processes. P2X4 has an established roles in this setting (Nat Med. 12:p133, 2006). Our recent research suggests that P2X7 plays a dominant role in this response (Kidney Int. 88:p1079, 2015; EBioMedicine 19:p73, 2017) by activating both immune and vascular cells during hypertensive arterial damage. This PhD focusses on P2X7 receptor function in the renal vasculature. In healthy arteries, P2X7 expression is typically restricted to the endothelial and adventitial layers. After hypertensive injury, P2X7 receptor expression becomes dysregulated and more widely expressed, implicating an important function in pathophysiology. Using a combination of informative in vivo models allowing lineage tracing and cell-specific receptor deletion, coupled with cell culture and molecular approaches, this exciting PhD will investigate the role of P2X7 receptors in a) renal endothelial:immune cell interface and b) the critical remodelling of the vascular smooth muscle layer following hypertensive injury.


The project will be supervised by Professor Matthew Bailey, shortlisted in 2018 by The Times Higher Education as Outstanding Research Supervisor of the Year and Professor Andrew Baker, an expert in vascular pathophysiology. The PhD student will join the Hypertension and Renal research theme in The Centre for Cardiovascular Science at The University of Edinburgh and be part of the University’s British Heart Foundation Research Excellence Award environment. The Centre houses ~80 PhD students and contributes to the vibrant postgraduate training environment on the Little France Campus. Additional, non-research training is supported by the Institute of Academic Development and career development of postgraduates is a priority of our research theme.

A major strength of the project comes from close research links with Professor Rafael Kramann, Chair of Nephro-Cardiology at RWTH, Aachen University. It is expected that the student will undertake part of the PhD training in the Kramman Lab (www.kramannlab.com). We are therefore looking for a motivated, knowledgeable and innovative student to develop this project. Previous relevant research experience will be an advantage.