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University of Leeds Featured PhD Programmes
FindA University Ltd Featured PhD Programmes

Obesity, HDL, endothelial function and vascular inflammation: A mechanistic study and the impact of metabolic surgery.


Faculty of Biology, Medicine and Health

About the Project

Obesity is a worldwide health issue of epidemic proportions and major cause of co-morbidities, including cardiovascular disease, diabetes, and other health conditions. Association between inflammation and obesity is well established. Macrophage numbers and pro-inflammatory gene expression are positively associated with adipocyte size. Inflammation plays a fundamental role in atherosclerotic plaque progression, vulnerability and thrombogenicity. The increase in adhesion molecule expression triggered by endothelial inflammation leads to leucocyte adhesion and release of pro-inflammatory cytokines, which in turn promote uptake of modified lipoprotein particles and formation of lipid-laden macrophage. As the inflammatory process continues, fibrogenic mediators and growth factors are released from activated leucocytes, resulting in smooth muscle proliferation and formation of atherosclerotic lesion. Endothelial dysfunction reported as an early marker for atherosclerosis which can be detected before structural changes to the vessel wall are apparent on angiography or ultrasound. Defect in the production or activity of nitric oxide (NO) leads to endothelial dysfunction. NO affect vascular health by inhibiting platelet aggregation and adherence, activation and recruitment of immune cells, smooth muscle proliferation, and oxidative modification of LDL; all of which forms the pathophysiological basis for atherosclerosis.
We showed that systemic and adipose tissue inflammation decrease significantly after bariatric surgery as well as hyperlipidaemia. In this project we will focus on vascular inflammation by deploying PET scanning and corneal endothelial cell structure.

The objectives of this PhD (or MD) project are to assess:
1-Impact of bariatric surgery on atheroma burden and inflammation of aorta in obese model of rats
2-Impact of bariatric surgery on vascular and adipose tissue inflammation, and corneal endothelial cell structure and integrity
3-Factors influence vascular inflammation in obesity
These studies have approval from the local ethics committee. The successful candidate will continue to recruit patients, train to undertake IVCCM and PET scans, and coordinate sample transfer and laboratory analysis, interpret the results and write papers. The successful candidate will have the opportunity to visit collaborating centres in Europe to learn new skills.

This project is suitable for medically qualified candidates, optometrists, scientists or qualified nurses with an interest in vascular disease, obesity or ophthalmology.

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select PhD Biochemistry.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk



Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

Rexrode KM, Carey VJ, Hennekens CH, Walters EE, Colditz GA, Stampfer MJ, et al. Abdominal adiposity and coronary heart disease in women. JAMA. 1998;280(21):1843-8. Epub 1998/12/10.

Lumeng CN, Saltiel AR. Inflammatory links between obesity and metabolic disease. J Clin Invest. 2011;121(6):2111-7. Epub 2011/06/03.

Yadav R, Hama S, Liu Y, Siahmansur T, Schofield J, Syed AA, France M, Pemberton P, Adam S, Ho JH, Aghamohammadzadeh R, Dhage S, Donn R, Malik RA, New JP, Jeziorska M, Durrington P, Ammori BA, Soran H. Effect of Roux-en-Y Bariatric Surgery on Lipoproteins, Insulin Resistance, and Systemic and Vascular Inflammation in Obesity and Diabetes. Front Immunol. 2017; 8: 1512.

Aghamohammadzadeh R, Greenstein AS, Yadav R, Jeziorska M, Hama S, Soltani F, Pemberton PW, Ammori B, Malik RA, Soran H, Heagerty. Effects of bariatric surgery on human small artery function: evidence for reduction in perivascular adipocyte inflammation, and the restoration of normal anticontractile activity despite persistent obesity. AM J Am Coll Cardiol. 2013; 62: 128-135.

Adam S, Liu Y, Siahmansur T, Ho JH, Dhage SS, Yadav R, New JP, Donn R, Ammori BJ, Syed AA, Malik RA, Soran H, Durrington PN. Bariatric surgery as a model to explore the basis and consequences of the Reaven hypothesis: Small, dense low-density lipoprotein and interleukin-6. Diab Vasc Dis Res. 2019; 16: 144-152.

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