Centre For Training In Clinical Cardiovascular And Cerebrovascular Research
Funder
National Health and Medical Research Council
Funding Amount
$2,000,000.00
Summary
This Centre proposes to expand its highly successful Centre of Clinical Excellence funded by NHMRC from 1998-2001. The Centre provided the opportunity in Western Australia for the highest quality clinical research training in comprehensive spheres relevant to the pathogenesis, prevention and therapeutics of cardiovascular disease, with an emphasis on the role of nutrition and lifestyle in relation to high blood pressure, arteriosclerosis, dyslipidaemia and the function of blood vessels. The new ....This Centre proposes to expand its highly successful Centre of Clinical Excellence funded by NHMRC from 1998-2001. The Centre provided the opportunity in Western Australia for the highest quality clinical research training in comprehensive spheres relevant to the pathogenesis, prevention and therapeutics of cardiovascular disease, with an emphasis on the role of nutrition and lifestyle in relation to high blood pressure, arteriosclerosis, dyslipidaemia and the function of blood vessels. The new Centre will broaden the scope of its research and training activities, through the inclusion of clinical projects related to heart failure, clinical and epidemiological research into cerebrovascular disease and stroke and research training opportunities with respect to clotting disorders and therapeutics for thrombosis.Read moreRead less
Performance And Safety Testing Of The BioQ Cardiac Assist System In A Chronic Ovine Heart Failure Animal Model
Funder
National Health and Medical Research Council
Funding Amount
$142,800.00
Summary
This proposal will test a novel cardiac assist system in safety and performance studies using a chronic sheep heart failure model. This device has been tested in cardiovascular simulators and in an acute animal model showing attractive proof-of-concept data. Specifically, the device increased left coronary artery blood flow and reduced aortic pulse and mean pressures using our novel self-powered fully implantable stand alone device, a potential therapy treatment for heart failure.
Targetting The NADPHoxidase Source Of Reactive Oxygen Species In Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$552,250.00
Summary
In Australia, coronary heart disease (CHD) leading to heart attacks or strokes is the largest cause of death, claiming a staggering 28,000 lives a year. Oxidative stress, resulting from increased production of oxygen free radicals in arteries, appears to be an important cause of CHD, heart attacks and strokes. We seek to understand how such oxyradicals are produced in the cells that make up the artery wall. Using novel DNA-type molecules we have recently discovered that a protein called Nox4 is ....In Australia, coronary heart disease (CHD) leading to heart attacks or strokes is the largest cause of death, claiming a staggering 28,000 lives a year. Oxidative stress, resulting from increased production of oxygen free radicals in arteries, appears to be an important cause of CHD, heart attacks and strokes. We seek to understand how such oxyradicals are produced in the cells that make up the artery wall. Using novel DNA-type molecules we have recently discovered that a protein called Nox4 is crucial for the production of oxygen free radicals by blood vessels. Furthermore, we have identified a class of drugs that selectively block the activity of Nox4 in blood vessels. We now wish to directly test whether inhibiting Nox4, either with DNA-type molecules, various drugs known to block Nox4, or by complete elimination of the Nox4 gene in mice, prevents the development of CHD in animal models. This work will not only advance our understanding of the origin of vascular oxidative damage but will also allow us to identify novel therapeutic targets in the treatment of cardiovascular diseases that are associated with increased oxidative stress. The same drugs and molecules might also prove useful for improving recovery from heart attacks and strokes, for Nox4 may be turned on in the heart and brain in these conditions. Information obtained in our study will be useful in directing future prescription practices in clinical management of CHD and stroke, and for designing new therapeutic compounds for CHD.Read moreRead less
A Factorial Randomised Trial Of Intensive Blood Pressure Lowering And Glucose Control In Subjects With Type 2 Diabetes.
Funder
National Health and Medical Research Council
Funding Amount
$303,330.00
Summary
People with diabetes are well known to be at high risk of developing major health problems earlier in life than people without diabetes. In particular, people with diabetes are more likely to suffer from heart attacks, stroke, blindness, kidney failure and leg ulcers that may lead to amputation. Studies of diabetics have shown that if blood pressure levels or glucose levels are uncontrolled, the risk of complications is much higher. Careful management of these two risk factors is therefore now a ....People with diabetes are well known to be at high risk of developing major health problems earlier in life than people without diabetes. In particular, people with diabetes are more likely to suffer from heart attacks, stroke, blindness, kidney failure and leg ulcers that may lead to amputation. Studies of diabetics have shown that if blood pressure levels or glucose levels are uncontrolled, the risk of complications is much higher. Careful management of these two risk factors is therefore now a cornerstone of diabetic care and there are well-established guidelines for treatment. However, there is new evidence to suggest that tighter control of blood pressure and glucose levels than is currently recommended might result in even greater benefits. ADVANCE (Action in Diabetes and Vascular Disease) is a large new study that has been designed by Australian researchers based at the Institute for International Health in Sydney. The aim of ADVANCE is to see if treatment to control blood pressure and glucose levels more tightly than usual reduces the risk of complications among adult diabetics. The study will include 10,000 individuals recruited from about 20 countries worldwide that will be followed for an average of 4.5 years. The first participants will be enrolled in April 2001 and the study results should be available by the end of 2006. There are presently about 300 million people in the world with diabetes and this number is increasing rapidly. The results of ADVANCE will therefore influence the care of a very large number of people. If the findings of the study were positive, implementation of the new treatments could be expected to prevent many tens of thousands of premature heart attacks and strokes around the world each year.Read moreRead less
The Effect Of Stress/strain And Fatigue Fracture Sites On Durability Of Modular Aortic Endografts And Arterial Walls
Funder
National Health and Medical Research Council
Funding Amount
$300,919.00
Summary
Aneurysmal disease is an age related phenomenon. The mean life expectancy of western populations has doubled in 100 years because of the reduction in deaths from preventable and treatable diseases, and prolongation of life with chronic and incurable diseases. The older community (>65 years) continues to be active and productive contrary to prior predictions. Aneurysmal disease has emerged as a result of the changing pattern of diseases in the community. As with many other diseases, prophylaxi ....Aneurysmal disease is an age related phenomenon. The mean life expectancy of western populations has doubled in 100 years because of the reduction in deaths from preventable and treatable diseases, and prolongation of life with chronic and incurable diseases. The older community (>65 years) continues to be active and productive contrary to prior predictions. Aneurysmal disease has emerged as a result of the changing pattern of diseases in the community. As with many other diseases, prophylaxis against aneurysmal disease is the most effective approach since 80% of those that rupture will result in death. Endoluminal grafting provides a much less invasive procedure and provides an attractive and elegant alternative to open surgery. The danger is that structural strengths will be compromised with failures due to lack of strength and inadequate device durability. The most practical endografts are those that are built up from modules but vulnerable sites affected by fatiguing and disruptive forces are being identified, in particular where a tube divides into two outflow channels – the bifurcation - and joins. To improve and protect the current device, and enable sound engineering for future devices, we need to know the nature, magnitude and location of these forces. The existing collaboration with medical specialist, Cook Aust., the Advanced Fluid Dynamics Laboratory (CSIRO, Melb.) and University of WA combines a multidisciplinary team working towards the design and durability of the next generation of endoluminal devices and percutaneous insertions. While Australia is at the forefront of development, its current place in the market can only be maintained by further product development. Optimising and improving endoluminal grafts will reduce the suffering of major surgery while prolonging a higher quality of life with a much less invasive procedure whose long-term effectiveness, and thereby acceptance is dependent upon reliable durability.Read moreRead less
Molecular Mechanisms Of Cardiac Function And Disease
Funder
National Health and Medical Research Council
Funding Amount
$10,053,131.00
Summary
Adult-onset heart disease remains the leading cause of death and disability in our society, with almost 2 million Australians affected. Furthermore, structural heart malformations are the most common type of abnormality at birth and the leading cause of deaths in infants dying from non-infectious causes. Many of these problems are due to defects in the development, repair and-or function of heart muscle cells or cardiomyocytes. Thus, we propose to understand, in fine detail, cardiomyocyte as wel ....Adult-onset heart disease remains the leading cause of death and disability in our society, with almost 2 million Australians affected. Furthermore, structural heart malformations are the most common type of abnormality at birth and the leading cause of deaths in infants dying from non-infectious causes. Many of these problems are due to defects in the development, repair and-or function of heart muscle cells or cardiomyocytes. Thus, we propose to understand, in fine detail, cardiomyocyte as well as integrated heart development, biology, physiology and function as a prerequisite for the development of major advances in the prevention and treatment of these disorders.Read moreRead less
Effects Of Risk Factor Control On Atherosclerosis, Vasoreactivity And Cardiac Ischemia In Patients On Dialysis
Funder
National Health and Medical Research Council
Funding Amount
$212,126.00
Summary
End-stage renal failure is one of the commonest serious chronic diseases; in Australia, over 10,000 patients are in dialysis programs or have functioning transplants. The commonest cause of death in this patient group is coronary artery disease, and attempts are routinely made to identify patients with this problem, with the intent of controlling this risk by angioplasty or bypass surgery. Unfortunately, these procedures may be less effective than usual, because the process of artery narrowing i ....End-stage renal failure is one of the commonest serious chronic diseases; in Australia, over 10,000 patients are in dialysis programs or have functioning transplants. The commonest cause of death in this patient group is coronary artery disease, and attempts are routinely made to identify patients with this problem, with the intent of controlling this risk by angioplasty or bypass surgery. Unfortunately, these procedures may be less effective than usual, because the process of artery narrowing is more aggressive in patients with renal disease. Moreover, this process may cause patients with negative testing for coronary disease at one point in time to develop coronary problems over follow-up. In this study, we propose to use a standard stress testing protocol to stratify the risk of coronary events in a group of at risk patients on dialysis. Those at highest risk will undergo bypass surgery, while those at intermediate and low risk will be randomized to usual care, or an aggressive treatment of atheroma with cholesterol reduction, folic acid supplementation (aiming to normalize homocysteine), blood pressure and blood sugar control. The effects of this approach will be followed by examination of biochemical markers of atherosclerosis, and imaging of arterial thickness and reactivity (reflecting tests of structure and function of the vasculature). We will also assess of the progression or reduction of abnormal cardiac stress responses, and the occurence of events at follow-up. Finally, follow-up data will be used to compare the predictive value of the 2 stress testing protocols. The results of this study will enhance our understanding of the importance of the atherosclerotic process in renal patients, and move the management approach for coronary disease in renal failure toward active risk factor control and away from revascularization.Read moreRead less
Inhibition Of C-Abl As A Target For Shortening Glycosaminoglycan Length On Proteoglycans And Preventing Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$500,750.00
Summary
The major health issue developing in Australia is vascular and cardiovascular disease resulting from obesity and diabetes. Whilst prevention strategies based on lifestyle changes are preferable, treating cardiovascular risk factors with the latest drugs has been shown to produce significant benefits but there is a large remaining component of disease. New therapies are required and these will most likely target blood vessels directly. We are working on the basic cause of atherosclerosis with the ....The major health issue developing in Australia is vascular and cardiovascular disease resulting from obesity and diabetes. Whilst prevention strategies based on lifestyle changes are preferable, treating cardiovascular risk factors with the latest drugs has been shown to produce significant benefits but there is a large remaining component of disease. New therapies are required and these will most likely target blood vessels directly. We are working on the basic cause of atherosclerosis with the aim of finding a mechanism and developing a drug to prevent the process - we have recently identified such a target and it is the subject of this research grant proposal. A group of very large molecules which have recently received increasing attention are the proteoglycans, combined protein-sugar molecules which are heavily coated with negatively charged groups. It has recently been published in the prestigious journal, Nature, that the binding of lipids in the blood to the wall of the blood vessel is the main cause of atherosclerosis. Proteoglycans are the molecules which cause the lipids to be stuck in blood vessels. Specifically, the length of the sugar (GAG) chains on the proteoglycan determines the binding of the lipids. We have now discovered a pathway and have one drug candidate which prevents the elongation of the GAG chains on proteoglycans. The exciting possibility is use of this agent with existing agents, for example, to use a statin drug to lower blood cholesterol and a new GAG elongation inhibitor to prevent the cholesterol sticking in the wall. The outcome will be the proof of the potential of a target for the direct therapy of atherosclerosis and a clear pathway for the development of a drug to be used in people susceptibility to atherosclerosis which is particularly people with diabetes.Read moreRead less