Biomarkers of Atherosclerosis
Academic site: Medicine, St Vincent's Hospital, Eastern Hill Campus
This project focuses on identification of novel biomarkers of atherosclerosis in human blood and tissue samples. Based on our previous studies, we expect to elaborate a range of novel low abundance proteins upregulated in atherosclerotic cardiovascular disease and to carefully investigate their clinical potential by analysing other established markers.
Once key proteins of interest are identified, levels will be measured in patient groups of interest using high throughput techniques to validate these findings and potentially lead to novel diagnostic tests for atherosclerosis that incorporate traditional and novel risk markers to maximise clinical utility.
Our preliminary data suggests that even in patients at high risk of atherosclerosis presenting for angiography, subgroups can be identified who are at significantly higher risk (up to 7 times). Positive findings in this study will greatly facilitate increased understanding of vascular risk and atherosclerosis pathophysiology. Particular focus will be made on inflammatory pathways since these appear to be highly involved at all stages of atherosclerosis pathophysiology.
This study will advance the use of novel technologies and approaches to the elucidation of as yet undefined proteins in CVD. Identification and characterisation of novel protein markers and integration into existing clinical paradigms will assist in development of better non invasive diagnostic tests for atherosclerosis, aid in targeted screening and therapeutic programmes and direct novel approaches to the investigation of disease pathways.
Hypothesis: That previously unrecognised plasma proteins in patients will be differentially expressed in patients with and without features of atherosclerosis and its complications and will be detected using novel plasma proteomic profiling techniques.
- Aim 1: To analyse differentially expressed proteins that will elucidate pathophysiological pathways in atherosclerosis identified in patients with and without atherosclerosis using extended plasma profiling.
- Aim 2: To confirm these findings in a similar cohort of patients at risk of atherosclerosis.
- Aim 3: To apply candidate biomarkers to established diagnostic and risk paradigms for atherosclerosis and its complications.
- Dr Amy Wilson-O'Brien, postdoctoral fellow
- Mr John Garlick, research assistant
- St Vincent's Institute of Medical Research
- Department of Mechanical Engineering, University of Melbourne
- St Vincent's Health Melbourne
- Australia Catholic University
- Walter & Eliza Hall Institute of Medical Research
- Sanson Institute
- RMIT University
- University of California San Francisco
- Stanford University
- Biogrid Australia, Data Linkage
- LAYLAND, J. J., WHITBOURN, R. J., BURNS, A. T., SOMARATNE, J., LEITL, G., MACISAAC, A. I., & WILSON, A. M. 2012. The index of microvascular resistance identifies patients with periprocedural myocardial infarction in elective percutaneous coronary intervention. Heart, 98, 1492-7.
- HOFFERBERTH, S. C., NEWCOMB, A. E., RYAN, M. C., YII, M. Y., NIXON, I. K., ROSALION, A., BOSTON, R. C., WARD, G. M., & WILSON, A. M. 2012. High incidence of insulin resistance and dysglycaemia amongst nondiabetic cardiac surgical patients. AnnThorac Surg, 94, 117 - 22.
- COOKE, J. P. & WILSON, A. M. 2010. Biomarkers of peripheral arterial disease. 2010. J Am Coll Cardiol, 55, 2017 - 23.
- WILSON, A. M., HARADA, R., NAIR, N., BALASUBRAMANIAN, N. M., & COOKE, J. P. 2007. L-arginine supplementation in peripheral arterial disease: no benefit and possible harm. Circulation, 116, 188-95.
- WILSON, A. M., KIMURA, E., HARADA, R. K., et al. 2007. Beta2-microglobulin as a biomarker in peripheral arterial disease: proteomic profiling and clinical studies. Circulation, 116, 1396 - 403.