Molecular mechanisms underlying the anti-atherogenic actions of natural products

Atherosclerosis, the underlying cause of myocardial infarction, stroke and peripheral vascular disease, is responsible for most deaths in the western world with mortality increasing at a marked rate in developing

countries. The economic burden from atherosclerosis and its complications is expected to worsen due to global increase in risk factors such as diabetes and obesity. Atherosclerosis is an inflammatory disorder of medium and large arteries regulated by key cytokines. Manipulating such inflammatory response represents a promising avenue for the prevention and treatment of this disease. Many natural products and their metabolites have anti-atherogenic properties though the underlying molecular mechanisms remain poorly understood. We are therefore investigating this aspect using a combination of in vitro and in vivo approaches. This project will focus on investigation of the protective actions of a chosen natural product or its metabolites on major processes implicated in atherosclerosis in vitro in the three key cell types associated with this disease (i.e., macrophages, endothelial cells and vascular smooth muscle cells) and in vivo using the low-density lipoprotein receptor deficient mouse model system (in collaboration with Dr. Timothy Hughes, School of Medicine, Cardiff University). These mice will be fed an atherogenic western-type diet for 12 weeks and 24 weeks supplemented with vehicle or natural product/metabolites. Parameters that will be analysed will include: body weight and weight of organs; plasma lipid profile; plaque morphometry, collagen deposition, and accumulation of macrophages, smooth muscle cells and T-lymphocytes (immunohistochemistry). In addition, RNA-sequencing will be used to determine global changes in gene expression. The effects on key signalling pathways (e.g., MAP kinases) will also be analysed. The studies will provide an in-depth understanding of anti-atherogenic actions of the natural product studied in vitro and in vivo.

Associate school School of Medicine.

Contact details for supervisor

Email - Ramji@Cardiff.ac.uk

Phone Number – 0044(0)2920876753

How to apply: 

You can apply online - consideration is automatic on applying for a PhD in Biosciences 

Please use our online application service at https://www.cardiff.ac.uk/study/postgraduate/research/programmes/programme/biosciences-phd-mphil-md  

Please specify that you are applying for this particular project and the supervisor.  

Information on the application process can be found here  

http://www.cardiff.ac.uk/study/postgraduate/applying