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Cai Read

Cai Read

BHF 4-Year Programme PhD Student


Research Interests

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.

Posters:

  • 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

Keywords

pulmonary arterial hypertension ; pulmonary hypertension

Key Publications

2016     

Read C, Fitzpatrick CM, Yang P, Kuc RE, Maguire JJ, Glen RC, Foster RE and Davenport AP.   Cardiac action of the first G protein biased small molecule apelin agonist. Biochem Pharmacol. 166:63-72.

Kennedy AJ, Yang P, Read C, Kuc RE, Yang L, Taylor EJ, Taylor CW, Maguire JJ, Davenport AP.       Chemerin Elicits Potent Constrictor Actions via Chemokine-Like Receptor 1 (CMKLR1), not G-Protein-Coupled Receptor 1 (GPR1), in Human and Rat Vasculature. J Am Heart Assoc. 14;5(10).

2017      

Yang P, Read C, Kuc RE, Buonincontri G, Southwood M, Torella R, Upton PD, Crosby A, Sawiak SJ, Carpenter TA, Glen RC, Morrell NW, Maguire JJ, Davenport AP.    Elabela/Toddler is an Endogenous Agonist of the Apelin APJ Receptor in the Adult Cardiovascular System, and Exogenous Administration of the Peptide Compensates for the Downregulation of its Expression in Pulmonary Arterial Hypertension. Circulation 135:1160-1173

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