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Targeting the CCL18-CCR8 axis to treat hypertension-associated end organ damage

Hypertension is a major cause of heart failure, heart attacks and strokes. Associated with the development of hypertension is the accumulation of macrophages in the arterial wall leading to fibrosis and vascular stiffening of central elastic arteries (i.e. aorta, carotid artery). This results in a reduced capacity of these vessels to buffer pulse pressure leading to peripheral vascular and end-organ damage. Whilst current antihypertensives are effective at lowering blood pressure, they don’t necessarily target vascular stiffening and as such new therapeutic approaches are sought. We have exciting new data to suggest that human macrophages release high concentrations of a chemokine, CCL18 which activates the G-protein coupled receptor, CCR8 leading to an elevation in blood pressure and associated end-organ damage. We hypothesise that pharmacological targeting of the CCL18-CCR8 axis will reverse hypertension and associated cardiovascular and renal fibrosis, and protect against end-organ damage. Project aim: The aim of this honours project is to assess the therapeutic utility of pharmacological targeting the CCL18-CCR8 axis to protect against hypertension and the associated end-organ damage. This study may lead to the development of more effective therapies for the treatment of hypertension and fibrosis in cardiovascular pathologies. Techniques: The project will utilize an angiotensin II-infusion model of hypertension in mice, and involve the measurement of blood pressure and ex vivo assays to assess vascular function (myography), detect inflammation (RT-PCR, superoxide detection), collagen generation (zymography, immunhistochemistry) and pro-fibrotic factors (ELISA).
Essential criteria: 
Minimum entry requirements can be found here:
hypertension, macrophage, chemokine, CCL18, end-organ damage
Biomedicine Discovery Institute (School of Biomedical Sciences) » Pharmacology
Available options 
Masters by research
Time commitment 
Top-up scholarship funding available 
Physical location 
Clayton Campus
Bradley Broughton
Robert Widdop

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