Sympathetic Nervous System Inhibition For The Treatment Of Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$455,365.00
Summary
One of the commonest consequences of diabetes is the development of renal impairment, in the worst case scenario resulting in renal failure reuqiring renal replacement therapy. We aim to test a novel therapeutic strategy based on inhibition of the sympathetic nervous system to halt progression of renal failure and to improve outcomes in patients with this condition.
Suppression Of NADPH Oxidase-derived Oxidative Stress By Anti-sense Probes And HDL In Human Vascular Endothelium
Funder
National Health and Medical Research Council
Funding Amount
$455,250.00
Summary
In Australia, coronary heart disease (CHD) causing heart attacks remains 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, is an important cause of CHD, heart attacks and strokes. We seek to understand how such oxyradicals are produced in the key cells that form the lining of all arteries, known as the vascular endothelium. By using novel DNA-type molecules (known as anti-sense) develo ....In Australia, coronary heart disease (CHD) causing heart attacks remains 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, is an important cause of CHD, heart attacks and strokes. We seek to understand how such oxyradicals are produced in the key cells that form the lining of all arteries, known as the vascular endothelium. By using novel DNA-type molecules (known as anti-sense) developed in our laboratory, which block a particular gene causing oxidative stress, we will determine whether this gene is responsible for the formation of oxyradicals in human and mouse cells grown in culture. In addition, we will explore whether this gene is turned on by factors known to be involved in CHD. Finally, we will also investigate whether the good cholesterol known as HDL can act to prevent oxidative stress in human cells, as we discovered it appears to do in living arteries in vivo. If we find it has the same protective effect in endothelium, we will determine how it does this, and which component proteins of the HDL particle are important. This might suggest new treatments to prevent acute events leading to heart attack and stroke, and possibly new applications where damage appears to result from acute oxidative stress, such as in the brain soon after a stroke has occurred. We also have a plan to develop antisense drugs that will target the important gene specifically in the affected endothelium. In addition, we have other specific new drugs that will block this system in arteries. Simultaneously we will be testing the role of this gene in mouse and rabbit models of artery disease, for both our types of drugs might provide valuable new therapeutic agents to target the underlying cause of CHD and not just its symptoms as current drugs do.Read moreRead less
Evaluation Of A Novel Electronic Decision Support Tool For Cardiovascular Risk Management - The TORPEDO Study
Funder
National Health and Medical Research Council
Funding Amount
$587,175.00
Summary
The TORPEDO study will test a new electronic decision support system that will help health professionals and patients navigate through the complexities of current clinical guidelines for treatments to help prevent heart attack, stroke and related conditions. The study will be conducted in 60 practices over 12 months, and if the system is found to be useful, this may prove to be helpful in the day-to-day management of all Australian adults when visiting their doctor.
Effects Of N-3 Polyunsaturated Fatty Acids On Post Surgical Atrial Fibrillation: A Prospective Randomised Study
Funder
National Health and Medical Research Council
Funding Amount
$536,529.00
Summary
Consumption of fish and fish oil has been associated with protective effects for deaths from heart disease in many studies. The effects are consistent and quite strong and appear to be unrelated to blood cholesterol levels. The effects are more likely due to the possibility that fish oil, which contains n-3 fats, can suppress abnormal heart rhythms which can cause 'sudden cardiac death'. This has been shown in animal studies, and recently we have shown that they can also suppress abnormal heart ....Consumption of fish and fish oil has been associated with protective effects for deaths from heart disease in many studies. The effects are consistent and quite strong and appear to be unrelated to blood cholesterol levels. The effects are more likely due to the possibility that fish oil, which contains n-3 fats, can suppress abnormal heart rhythms which can cause 'sudden cardiac death'. This has been shown in animal studies, and recently we have shown that they can also suppress abnormal heart rhythms in humans. Patients undergoing coronary bypass surgery are particularly susceptible to abnormal heart rhythms in the upper chambers of the heart in the days immediately following surgery. While these abnormal rhythms are rarely life threatening, they can result in increased post-surgical complications and a longer hospital stay with associated increased costs to the health system. In this study we will determine whether providing high dose fish oil for 3 weeks immediately preceding coronary bypass surgery, will result in a reduction in the proportion of patients experiencing post-surgical abnormal heart rhythms. We will also examine the effects of n-3 fats on the incidence of other complications following bypass surgery and also the length of hospital stay. In addition, we will gather data which will provide insight into the mechanisms by which n-3 fatty acids produce their well documented benefits to patients with cardiovascular disease. The significance of this study is its ability to provide a protective strategy in heart disease in which the mechanism is understood, which is effective, and importantly, which will have the potential to provide savings to the health care system through a reduction in hospital stay.Read moreRead less
Exertional Dyspnoea With Increased Filling Pressure - Mechanisms And Treatment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$387,793.00
Summary
Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and theref ....Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and therefore, outcome) than with late stage disease. Current treatment strategies are expensive and because they are directed at end-organ damage (heart failure, heart attacks etc), rather ineffective. This multispecialty, multidisciplinary group will undertake a series of unique studies aimed at identifying early cardiovascular disease. The strategy will involve detection of abnormal filling behaviour at stress echocardiography, with randomization into longterm and short-term trials to examine various therapeutic strategies. Sensitive new cardiovascular imaging techniques will be used to detect preclinical abnormalities in the structure and function of the heart and vasculature, facilitating a mechanistic understanding of the process of increasing filling pressure with exercise.Read moreRead less
Linking Early Heart Growth Stress And Adult Cardiopathology: A New Role For Autophagy
Funder
National Health and Medical Research Council
Funding Amount
$524,013.00
Summary
An enlarged heart at maturity is a major risk factor. The goal of this project is to understand how cardiac growth abnormality in the neonate contributes to adult growth pathology. We have recently discovered that a type of stress-triggered cell death (autophagy) is increased in rodent neonatal hearts which later become enlarged, and that this cell death is regulated by the hormone angiotensin II. We will study the mechanisms involved to identify intervention opportunities to normalize growth.
A Dual Antigen Synthetic Peptide Subunit Vaccine Approach To Prevent Streptococcal Associated Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$604,017.00
Summary
Infection with streptococcus is responsible for causing more than 500,000 deaths each year, the majority of which are due to rheumatic fever and rheumatic heart disease, which contributes to cardiovascular disease. Our research is aimed at the development of a vaccine to prevent heart disease and involves targeting multiple molecules present on the bacterial surface. We will use a novel vaccine delivery system developed in the laboratory, which will enable the vaccine to be delivered nasally.
Ischaemia-induced Sarcolemmal Changes And Their Role In Ins(1,4,5)P3 Generation And Arrhythmogenesis
Funder
National Health and Medical Research Council
Funding Amount
$468,750.00
Summary
Studies in our laboratory at the Baker Heart Research Institute over the last several years have identified a novel mechanism causing the development of arrhythmias, a primary cause of sudden cardiac death in heart failure as well as during an acute heart attack caused by acutely reduced blood flow. The reduced blood flow leads to lowered oxygen and nutrients and thus the beating heart cells have insufficient energy to properly maintain function. Under these stressed conditions, cardiac myocytes ....Studies in our laboratory at the Baker Heart Research Institute over the last several years have identified a novel mechanism causing the development of arrhythmias, a primary cause of sudden cardiac death in heart failure as well as during an acute heart attack caused by acutely reduced blood flow. The reduced blood flow leads to lowered oxygen and nutrients and thus the beating heart cells have insufficient energy to properly maintain function. Under these stressed conditions, cardiac myocytes produce large amounts of a small molecule called IP3, which interferes with the normal electrical balance of the cells. Blocking IP3 generation prevents arrhythmias under these acutely ischaemic conditions. In more recent studies, we have identified many of the enzymes responsible for generation of IP3 in heart cells and have defined the properties of the regions of the cell responsible for this response. We now want to establish exactly how a period of ischaemia alters the localization or functioning of the enzymes that are responsible for this pathological change that leads to fatal arrhythmias.Read moreRead less
Role Of Sympathetic Nervous System In The Development Of Early Organ Damage In Obesity:an Emerging Target For Therapy
Funder
National Health and Medical Research Council
Funding Amount
$544,534.00
Summary
Young people with obesity often have no signs of cardiovascular disease but their organs, such as the heart, the kidneys and the blood vessels present early evidence of damage that can, in time, progress to confer cardiovascular risk. This study will look at the potential beneficial effect of a drug, by itself or in association with a low calorie diet, in reversing the progression of organ damage in young obese subjects.
Differences Between Physiological And Pathological Cardiac Hypertrophy Offer New Strategies For Treating Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$335,473.00
Summary
The heart becomes large both in athletes as well as in patients with heart disease and failure. In the first instance, the large (hypertrophied) heart has normal or even increased pumping ability (function) whereas in the patient with heart disease the function is depressed and the heart may fail. My studies are directed towards finding out what is the difference in these 2 situations and what mechanisms are responsible for making one big heart pump well and the other big heart pump poorly. Spec ....The heart becomes large both in athletes as well as in patients with heart disease and failure. In the first instance, the large (hypertrophied) heart has normal or even increased pumping ability (function) whereas in the patient with heart disease the function is depressed and the heart may fail. My studies are directed towards finding out what is the difference in these 2 situations and what mechanisms are responsible for making one big heart pump well and the other big heart pump poorly. Specifically my project hopes to identify the genes and proteins responsible for the differences. I have already identified one such gene and I now plan to manipulate this gene by overexpressing it in animals (transgenic mice) with heart failure. I predict that overexpression of this gene will improve heart function in models of heart failure. If the hypothesis is correct, activating genes that are activated in the athlete's heart maybe a potential tool for improving heart function, quality of life and life span in patients with heart failure.Read moreRead less