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Cambridge Cardiovascular



Supervisor: Prof Julian Griffin

Title: A metobolomic analysis of celecoxib and rofecoxib administration in mice

Abstract: Experimental evidence suggests an increase in adverse cardiovascular events associated with Rofecoxib use, and to a lesser degree in some but not all Coxibs and NSAIDs. Given the ambiguity of the clinical data, and to determine whether the adverse cardiovascular events seen with rofecoxib represent a class effect, focus has shifted to the elucidation of putative mechanisms of these side-effects.

My PhD project forms part of the exploratory, hypothesis generating, phase of PENTACON. The objective of the first year of work was to determine whether therapeutic concentrations of celecoxib and rofecoxib elicit distinct metabolomics effects in vivo in mice. Biofluids and tissue were profiled by a range of metabolomic tools, including Nuclear Magnetic Resonance (NMR) Spectroscopy, Gas Chromatography – Mass Spectrometry (GC-MS) and Liquid Chromatography – Mass Spectrometry (LC-MS).

In years 2 and 3 this project will focus in on some of the most interesting preliminary results, whilst also extending the investigation to include naproxen in the analysis. The ultimate objective of this work is hypothesis generation and mechanism elucidation of the COX-2 associated adverse cardiovascular events.

BHF Centre of Excellence PhD Student