Supervisor: Dr Anthony Davenport
Title: Development of Biased Apelin Agonists for the Treatment of Pulmonary Arterial Hypertension
Abstract: Pulmonary Arterial Hypertension (PAH) is a devastating disease with few effective treatments and high mortality rates. It is characterised by complex remodelling of the pulmonary vasculature leading to increased pulmonary pressures, right ventricular hypertrophy and ultimately right ventricular failure. Apelin, an endogenous peptide, associated with vasodilatation and cardiac inotropy is downregulated in the disease, meanwhile administration to various animal models is beneficial. We hypothesise that an apelin agonist could replace the endogenous peptide, providing a novel treatment for PAH. However, the apelin receptor is rapidly internalised through the β-arrestin pathway. A biased agonist towards the G-protein pathways could avoid internalisation, thus, providing a longer duration of action and reduced chance of patients becoming refractory. We aim to develop biased apelin agonists to be tested in various assays in vitro, ex vivo and in vivo to comprehensively assess their potential as therapeutics for PAH.
- Characterisation of apelin receptor agonists in clinically relevant human tissue. Cai Read, Christopher Fitzpatrick , Akash Gandhi , Rhoda E. Kuc, Peiran Yang, Janet J. Maguire, Robert Glen, Richard Foster, Anthony P. Davenport. Poster Presentation at the British Pharmacological Society focused meeting Exploiting new pharmacology and application to drug discovery in Edinburgh and Physiology 2015 in Cardiff
pulmonary arterial hypertension ; pulmonary hypertension