Characterisation of novel inhibitors of vascular injury due to inflammation
Fact file
| Duration |
Three to four years full-time |
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| Eligibility |
Self-funded; Home, EU or International Students |
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| Supervisor(s) |
Dr Vera Ralevic
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| Application deadline |
No deadline |
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About the project
Myeloperoxidase (MPO) is a haemoprotein that is highly expressed in neutrophils and is secreted during injury and inflammation to assist in host defence reactions by producing antimicrobial reactive oxygen species. However, in pathological conditions persistent production of MPO-derived oxidants contributes to tissue damage. Elevated MPO and its oxidants are markers of inflammation, and elevated MPO levels predict adverse outcome in patients with heart disease. The identification and characterisation of drugs which can inhibit the actions of MPO and scavenge HOCl is clearly desirable.
This project will use a novel in vitro model of vascular dysfunction involving MPO and porcine isolated coronary arteries to determine the potential of hydrogen sulphide (H2S)-releasing compounds as therapeutic agents in cardiovascular disease. Arteries will be incubated with MPO followed by an assessment of their vasomotor function using a pharmacological approach. H2S donors, including a novel compound, GYY4137, which acts as a slow-releasing H2S donor, will be investigated as potential vasoprotective agents. Their effects will be compared with those of known MPO inhibitors. Direct vasomotor actions of the compounds will be investigated. H2S-mediated inhibition of MPO activity will also be measured using a biochemical assay. This project is part of a broader research interest within the laboratory on the effects of H2S in the cardiovascular system. The student will be trained in all aspects of the research.
Funding notes
This project is available to self-funded students. Home applicants should contact the supervisor to determine the current funding status for this project. EU applicants should visit the Graduate School webpages for information on specific EU scholarships. International applicants should visit our International Research Scholarships page for information regarding fees and funding at the University.
References
- Rayment et al (2007). FASEB J, 21,577-585.
- Palinkas et al (2014). Br J Pharmacol. 172, 1516–1532.
See this project on FindaPhD
Characterisation of novel inhibitors of vascular injury due to inflammation