I am a translational, human physiologist which places me in a unique position to address important clinical questions. My current interests centre on: • Identification of novel predictors of unstable coronary heart disease • Novel treatment approaches in:
Angiopoietin-2, Aortic Inflammation And Cardiovascular Events
Funder
National Health and Medical Research Council
Funding Amount
$332,161.00
Summary
Based on detailed preliminary data, we plan to investigate the importance of a novel protein (the cytokine angiopoietin-2) in cardiovascular disease. The results of this study will clarify the role of this cytokine in vascular pathology and may provide an important target for novel therapy and-or diagnostic markers for cardiovascular disease progression.
Urine Proteomics As A New Diagnostic Approach For Cardiovascular Risk And As A Discovery Tool For Novel Pathomechanisms In Atherosclerotic Disease
Funder
National Health and Medical Research Council
Funding Amount
$69,500.00
Summary
Atherosclerosis (hardening of blood vessels) followed by blockage is the leading cause of death due to heart attacks and strokes. Up until now there has been no simple tests to predict this reliably.The outcome of this project will give us a better understanding of atherosclerosis and provide a simple non-invasive urine test to detect atherosclerosis which would lend clinicians the opportunity to intervene early.
The Role Of New Generation Multidetector Row CT For Identification And Management Of Vulnerable Plaque At Risk Of Acute Coronary Syndrome : A Prospective Observational And Interventional Study
Funder
National Health and Medical Research Council
Funding Amount
$189,326.00
Summary
Heart attack remains one of the major cause of death. This is usually due to rupture of a plaque (due to cholesterol buildup) in the major heart arteries. Studies using invasive ultrasound have identified some features of plaque that are at high risk of rupture. These plaques are referred to as "vulnerable plaque". Recent developments in the computed tomography (CT) technology which is a non-invasive technique has enabled us to also identify these features. However thus far, no prospective large
Development Of A Catheter-based Device For The Detection Of Vulnerable Atherosclerotic Plaques
Funder
National Health and Medical Research Council
Funding Amount
$560,582.00
Summary
Atherosclerosis (hardening of blood vessels) is a major cause of disability and death worldwide. These lesions can suddenly become unstable leading to rupture and the occlusion of blood vessels with catastrophic complications such as heart attacks and strokes. Our project aims to develop a novel invasive imaging system to reliably detect these unstable lesions before they cause complications so that preventive measures can be taken, potentially saving many lives.
A Study Of The Plaque-modifying Actions Of Colchicine In Stable And Unstable Atherosclerosis: From Mouse Models To Clinical Imaging.
Funder
National Health and Medical Research Council
Funding Amount
$1,198,460.00
Summary
Inflammation causes the plaques in arteries that cause heart attacks and strokes. There is major interest in developing drugs that reduce this inflammation for patients with heart disease. We are studying the effects of colchicine, an anti-inflammatory drug used to treat the joint disease, gout, in order to see whether it also prevents the build up of plaques and their progression to heart attacks and strokes.
Preventing Myocardial Infarction: A Mouse Model Of Atherosclerotic Plaque Instability/rupture As Unique Tool For Establishing Novel Pharmacological Strategies And Targeted Molecular Imaging
Funder
National Health and Medical Research Council
Funding Amount
$586,965.00
Summary
Myocardial infarction strikes without warning and thereby causes death or major disability. It is typically caused by sudden rupture of atherosclerotic plaques and occlusion of coronary arteries. Research on this was hampered by the lack of an animal model of plaque rupture. We have newly established a mouse model, which we will now use to generate novel tools to image and identify plaques that are prone to rupture and to develop novel therapies preventing plaque rupture and myocardial infarctio ....Myocardial infarction strikes without warning and thereby causes death or major disability. It is typically caused by sudden rupture of atherosclerotic plaques and occlusion of coronary arteries. Research on this was hampered by the lack of an animal model of plaque rupture. We have newly established a mouse model, which we will now use to generate novel tools to image and identify plaques that are prone to rupture and to develop novel therapies preventing plaque rupture and myocardial infarction.Read moreRead less
Damage To Arterial Extracellular Matrix Induced By Reactive Nitrogen Species And Its Consequences
Funder
National Health and Medical Research Council
Funding Amount
$326,250.00
Summary
It is well established that lipids accumulate in the artery wall during the development of atherosclerosis (hardening of the arteries), and that much of this lipid arises from low-density lipoproteins (LDL). The uptake of cholesterol and lipids from LDL by cells present in the arterial wall is normally tightly regulated and under feedback control, but modification of the LDL particles can result in their recognition by the scavenger receptors of macrophage cells and unregulated accumulation of l ....It is well established that lipids accumulate in the artery wall during the development of atherosclerosis (hardening of the arteries), and that much of this lipid arises from low-density lipoproteins (LDL). The uptake of cholesterol and lipids from LDL by cells present in the arterial wall is normally tightly regulated and under feedback control, but modification of the LDL particles can result in their recognition by the scavenger receptors of macrophage cells and unregulated accumulation of lipids within such cells. The formation of these lipid-laden (foam) cells is a hallmark of atherosclerosis. Whilst this lipid accumulation is undesirable, if the resulting lesions are stable they are of less concern than those that are unstable and prone to rupture. Rupture of lesions and consequent blood clot formation (thrombosis) are a prime cause of sudden heart death and stroke. Despite considerable effort the reasons for plaque rupture are poorly understood. This study will investigate one potential mechanism by which lesions might become destabilised and prone to rupture. We will investigate the role of reactive intermediates in inducing damage to the extracellular matrix. Reactive intermediates are known to be generated by inflammatory cells, and it is well established that these cells are present at elevated levels in lesions. The extracellular matrix is responsible for maintaining the 3-dimensional structure of biological systems including the artery wall, and damage or fragmentation of this material may weaken this scaffolding and make the lesions prone to rupture. We will also examine how such matrix damage affects the behaviour of cells within lesions. A detailed knowledge of which processes are important in lesion rupture is an essential prerequisite to the development of new therapeutic strategies.Read moreRead less
Myeloperoxidase-catalysed Damage To Arterial Extracellular Matrix And Its Consequences
Funder
National Health and Medical Research Council
Funding Amount
$384,750.00
Summary
A heme enzyme (myeloperoxidase) has been shown to be present in the lesions present in diseased human arteries, and it has been reported that this enzyme contributes to the development of arterial disease via its ability to catalyse the formation of highly reactive oxidants. Recent studies have shown that the level of this enzyme correlate strongly with the presence of coronary artery disease, and that this enzyme may play a role in plaque rupture, a leading cause of sudden coronary death. It ha ....A heme enzyme (myeloperoxidase) has been shown to be present in the lesions present in diseased human arteries, and it has been reported that this enzyme contributes to the development of arterial disease via its ability to catalyse the formation of highly reactive oxidants. Recent studies have shown that the level of this enzyme correlate strongly with the presence of coronary artery disease, and that this enzyme may play a role in plaque rupture, a leading cause of sudden coronary death. It has also been reported that elevated levels of metal ions are present in advanced human atherosclerotic lesions. In recent experiments we have shown that products generated by myeloperoxidase can interact with metal ions and superoxide radicals, and that this process results in an exacerbation of damage. This synergism between the oxidants generated by myeloperoxidase and metal ions may explain, at least in part, the complex mixture of products detected in human lesions and be responsible for the weakening of lesion structure and contribute to an enhanced likelihood of plaque rupture. This study will examine the potential effects and mechanisms of damage to extracellular matrix materials from normal arteries and cultured cells We will examine under what circumstances interactions occur and whether these reactions may play a key role in plaque rupture. We will also examine how materials arising from damage to the extracellular matrix may affect the cells whic grow upon this scaffolding, and whether this may be partly responsible for altered behaviour of cells within dveloping atherosclerotic lesions. A detailed knowledge of which processes are important in plaque rupture is an essential pre-requisite to the development of new therapeutic strategies.Read moreRead less