Effect of uraemic toxins of vascular reactivity

Research Opportunity
Honours, Master of Biomedical Science
Number of Honour Places Available
1
Department
Medicine and Radiology
Location
St Vincent's Hospital
Group Leader Email Number Webpage
Dr Andrew Kompa akompa@unimelb.edu.au Personal web page
Primary Supervisor Email Number Webpage
Dr Amanda Edgley aedgley@unimelb.edu.au Personal web page

Project Details

Cardiovascular disease in the setting of chronic kidney disease (CKD) displays unique characteristics, primarily left ventricular (LV) hypertrophy with extensive interstitial fibrosis as well as endothelial dysfunction, arterial stiffness, calcification and inflammation, collectively termed ‘uraemic cardiomyopathy’. Uraemic toxins are elevated in the circulation of patients with CKD, and due to their strong binding affinity to serum proteins (ie albumin), they are unable to be removed from the circulation even by conventional dialysis, being too large to pass through the pore o the dialysis membrane.

Indoxyl sulphate (IS), a derivative of tryptophan metabolism, is one such uraemic toxin that has been extensively examined in cells and animal models of disease. IS has been demonstrated to exert deleterious effects in cardiac, renal, vascular and immune cells, and in tissues from man and animal models.

Recently, tryptophan metabolites such as IS and kynurenic acid (KA, also a protein bound uraemic toxin) were identified as ligands for the aryl hydrocarbon receptor (AhR), a cytosolic ligand-dependent transcription factor that mediates numerous biological processes including inflammation, vascular remodeling, and atherosclerosis. Activation of this receptor is known to target the oxidative stress pathway by both genomic and non-genomic mechanisms.

This project will assess the vascular reactivity of aortic vessels exposed to the uraemic toxins IS and KA in rat and human vascular tissue, and examine its inhibition using selective AhR antagonists. The tissue will be examined for changes in protein and gene expression using immunohistochemistry and real time PCR. This project will potentially identify a novel agent to treat vascular and inflammatory changes in patients’ with CKD.

This project is suited for an Honours/Masters research project.


School Research Themes

Cardiometabolic



Research Opportunities

Honours, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department

Medicine and Radiology

Research Group / Unit / Centre

Biomedical Translational Research Group: Developing Therapies for Cardiovascular Disease

Research Node

St Vincent's Hospital

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