Vascular Biology Laboratory - Honours in 2009

An Honours project undertaken in this lab would be administered by the Discipline of Pathology.

Our laboratory focuses upon protein modifications that potentially underlie the severity of acute myocardial infarct in hearts from diabetic rats. Additionally, we have an established interest in monitoring oxidative stress in disease states including atherosclerosis, acute renal failure and cerebral ischemia injury (stroke).

We use the tools of proteomics to investigate markers of heart disease and the post-translational modification of proteins resulting from cardiovascular disease in diabetics and kidney disease in burns patients. We have established an animal model of diabetic cardiomyopathy and will use this model to assess changes in key cardiac proteins resulting from experimental heart attack. Specific techniques include liquid chromatography, 1D and 2D electrophoresis, mass spectrometry coupled with peptide mass mapping.

Recent interesting publications:

Hypochlorous acid oxidizes methionine and tryptophan residues in cardiac myoglobin. A. Szuchman-Sapir, D.I. Pattison, N.A. Ellis, C.L. Hawkins, Mi.J. Davies, P.K. Witting. Free Radic Biol Med. 2008 Submitted (available on request from PW)

Parry SN, Ellis N, Li Z, Maitz P, Witting PK. Myoglobin induces oxidative stress and decreases endocytosis and monolayer permissiveness in cultured kidney epithelial cells without affecting viability. Kidney Blood Press Res. 2008;3:16-28.

Bhindi R, Witting PK, McMahon AC, Khachigian LM, Lowe HC. Rat models of myocardial infarction. Pathogenetic insights and clinical relevance. Thromb Haemost. 2006;96:602-610.

Witting P.K., Harris H.H., Rayner B.S., Aitken J.B., Dillon C.T., Stocker R., Lai B., Cai Z., and Lay P.A. The Endothelium-derived Hyperpolarizing Factor, H2O2, Promotes Metal-ion Efflux in Aortic Endothelial Cells: Elemental Mapping by a Hard X-ray Microprobe. Biochemistry, 2006, 45, 12500-12509.

Rayner B.S., Duong T.T.H., Myers S.J., Witting P.K. Protective effect of a synthetic antioxidant on neuronal cell apoptosis resulting from experimental hypoxia re-oxygenation injury. J. Neurochem. 2006, 97, 211-21.

Hack B., Witting P.K., Rayner B.S., Stocker R., and Headrick J.P. The relation between oxidant stress and damage and myocardial injury in post-ischemic mouse hearts: Effects of adenosine and pyruvate. Mol. Cell. Biochem., 2006, 287, 165-175.

Benson VL, McMahon AC, Lowe HC, Khachigian LM. The streptozotocin-treated Sprague-Dawley rat: a useful model for the assessment of acute and chronic effects of myocardial ischaemia reperfusion injury in experimental diabetes. Diab Vasc Dis Res. 2007;4:153-4.

Post translational changes to key cardiac proteins in the hearts of diabetic rats after experimental heart attack

Supervisor + contact details:

• Dr Paul Witting
• Dr Aisling McMahon

The major causes of morbidity and mortality in diabetes are the cardiovascular complications of the disease. Of these, the development of diabetic cardiomyopathy is of particular concern, as it increases the risk and severity of acute myocardial infarction (heart attack) compared with the general population. The proposed project will provide information on the role for oxidative stress and inflammation in promoting the severity of myocardial infarct in an animal model of diabetic cardiomyopathy. We plan to use an established rat model of diabetes and monitor post translational changes to key cardiac proteins through a proteomic approach combining 2D gel and mass spectrometry peptide mass mapping. An understanding of the role for oxidative stress and inflammation following acute myocardial infarct in diabetics may allow the development of new therapeutic approaches targeted at slowing down the progression of cardiomyopathy and thereby potentially improving heart function and quality of life in diabetes sufferers. This would be viewed as a major advance.