Exercise As Medicine For Heart Failure: A Novel Intervention To Improve Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$665,585.00
Summary
Heart failure (HF) is a common, debilitating and expensive disease; prognosis remains poorer than for the most cancers. 30,000 Australians are diagnosed every year and 300,000 live with the HF, at an annual cost of ~$1Billion. Exercise training is effective therapy in HF, because it reverses many of the problems that contribute to the reduced lifespan and impaired quality of life of patients with HF. We will test an exciting new type of exercise that promising greater benefit, at lower risk.
Developmental Origins Of Adult Cardiovascular Disease: Vascular Health In The Raine Cohort
Funder
National Health and Medical Research Council
Funding Amount
$1,087,427.00
Summary
The Raine study is a unique long term experiment that has collected extensive pre-birth and childhood data in ~3000 young Australians, who are now 27 years old. We plan to measure the artery health of 1200 of these volunteers and to determine what factors, both before and after birth, influence the presence of early atherosclerosis in humans. This study will guide strategies aimed at early prevention of heart attacks and stroke in humans, by defining the major risk factors.
Role Of Epigenomic Changes In Conferring Hyperglycemic Memory
Funder
National Health and Medical Research Council
Funding Amount
$636,146.00
Summary
The major burden of type I diabetes remains its vascular complications including diabetes-accelerated athersclerosis. Despite improved glucose control, diabetic individuals develop complications as a result of prior poor glycemic control. Although the development and progression of these diabetic complications is strongly associated with mean levels of glucose, recent studies suggest that the deleterious effects of early exposure to high levels of glucose persist for years even after treatment h ....The major burden of type I diabetes remains its vascular complications including diabetes-accelerated athersclerosis. Despite improved glucose control, diabetic individuals develop complications as a result of prior poor glycemic control. Although the development and progression of these diabetic complications is strongly associated with mean levels of glucose, recent studies suggest that the deleterious effects of early exposure to high levels of glucose persist for years even after treatment has returned glucose levels towards normal.Read moreRead less
A-Prof Wheatley is a respiratory and sleep disorders physician investigating the pathogenesis, health consequences and management of sleep breathing disorders, including sleep apnoea and snoring.
Identification Of Heterogeneity In Vasodilator Function In Human And Rat Resistance Vessels: Potential Drug Targets?
Funder
National Health and Medical Research Council
Funding Amount
$595,330.00
Summary
The balance between the ways that blood vessels decrease in size (constrict) and increase in size (dilate) determine how blood vessels normally function. There are many differences in the ways that blood vessels control this balance in different parts of the body. Such differences are altered in vascular diseases, such as hypertension and diabetes, which are prevalent in obesity, such that constriction generally outweighs dilation. However, what these differences are and how they occur are not w ....The balance between the ways that blood vessels decrease in size (constrict) and increase in size (dilate) determine how blood vessels normally function. There are many differences in the ways that blood vessels control this balance in different parts of the body. Such differences are altered in vascular diseases, such as hypertension and diabetes, which are prevalent in obesity, such that constriction generally outweighs dilation. However, what these differences are and how they occur are not well understood. While current drugs for treating vascular disease either reduce vessel constriction or increase dilation, they are not specific for individual arteries; a situation that would allow us to control vascular diseases in a very specific manner. Recently, we have described differences between the ways that individual vessels are controlled. These changes relate to differences in the way that different vessels dilate. AIMS - To further understand normal blood vessel function and the changes that occur in blood vessels in cardiovascular disease, with a focus on the ways that blood vessels dilate in normal states and in obesity-related diseases, such as in hypertension and diabetes. - The eventual aim is to identify the specific ways that arteries function, so that artery-specific drug targets can be identified to treat disease-related changes in cardiovascular disease in a very specific manner. EXPECTED OUTCOMES This project will contribute to understanding blood vessel function in health and disease. The expected eventual outcome is the identification of the mechanisms that underlie the function of different arteries in different parts of the body, so that specific individual vessel function can be targeted to treat vascular disease. Additionally, this work will also verify the relevance of the diet-induced obesity animal model, in terms of the characteristics and causes of human obesity and related cardiovascular disease.Read moreRead less
Regulation Of VEGFR Trafficking And Signal Transduction By The Ubiquitin Ligase Nedd4
Funder
National Health and Medical Research Council
Funding Amount
$388,347.00
Summary
Our recent work has discovered that the Nedd4 gene is crucial for the growth and development of blood vessels and lymphatic vessels. Our data suggest that Nedd4 controls vessel growth by regulating the levels and signalling activity of the key vascular growth factor receptors VEGFR-2 and VEGFR-3. The goals of this proposal are to define precisely how Nedd4-1 regulates the activity of these receptors and how VEGFR signalling could be better targeted to treat vascular disorders.
The Role Of Snoring Vibrations In The Pathogenesis Of Early Carotid Artery Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$593,833.00
Summary
Habitual snoring is a very common problem in the adult population, with a prevalence of between 20-40%. Increasingly it is now recognised that snoring may be an independent risk factor for the development of stroke. In this proposal, we will explore the hypothesis that chronic snoring transmits a pressure wave through the tissues of the neck to the carotid artery which may damage the artery wall and subsequently lead to stroke. This may lead to new strategies to treat habitual snoring.
An Extended Follow-up Of Stroke Patients For Cognitive Impairment And Neuropsychiatric Disorders: Sydney Stroke Study
Funder
National Health and Medical Research Council
Funding Amount
$321,800.00
Summary
Vascular Dementia (VaD) is the second most common cause of dementia after Alzheimer's disease. In fact, it may be a preventable cause of dementia. Yet it has been relatively neglected by researchers until the last decade, which has seen an upsurge of interest in this disorder. There is no consensus on the criteria for dementia. The profile of early cognitive impairment due to vascular factors is still poorly understood, and the longitudinal course of VaD as defined by modern criteria has not bee ....Vascular Dementia (VaD) is the second most common cause of dementia after Alzheimer's disease. In fact, it may be a preventable cause of dementia. Yet it has been relatively neglected by researchers until the last decade, which has seen an upsurge of interest in this disorder. There is no consensus on the criteria for dementia. The profile of early cognitive impairment due to vascular factors is still poorly understood, and the longitudinal course of VaD as defined by modern criteria has not been studied. There have been few studies of the progressive changes in MRI in patients with cerebrovascular disease. The overlap of VaD and Alzheimer's disease (AD) remains a problem for taxonomists and clinicians. One approach to the study of VaD is to examine a high risk group of subjects longitudinally to determine the early features, the risk factors and progressive changes. With this in mind, we began studying a cohort of stroke patients who are at high risk of VaD, in 1997-1999, and are following them longitudinally. The follow-up is now in its third year, and three neuropsychological assessments and two MRI-MRS scans have been performed. We propose to extend the follow-up to 5 years, with repeat neuropsychiatric, neuropsychological and MRI-MRS investigations, and wherever possible to necropsy, to determine the nature of vascular pathology that underlies cognitive impairment. Our cohort of stroke patients is arguably the most comprehensively assessed such cohorts internationally, and presents an excellent opportunity for a long-term follow-up study.Read moreRead less
Role For Zinc And ZIP2 In The Action Of Nitric Oxide And In Vascular Protection Against Cigarette Smoke And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$685,941.00
Summary
The NO/cGMP signalling pathway, which is central to cardiovascular physiology and protection against disease, is only fully effective when there are adequate levels of zinc in the vascular endothelium. This is especially important where zinc stores are depleted (elderly, smokers, diabetics and kidney disease). There is an urgent clinical need to implement strategies to monitor vascular Zn status. This application will explore the underlying science and translate these to the clinic.
Defining The Role Of The Ubiquitin Protein Ligase Nedd4 In Vascular Development.
Funder
National Health and Medical Research Council
Funding Amount
$702,166.00
Summary
Blood and lymphatic vessels are vital components of the cardiovascular system. Abnormalities in the growth and development of these vessels are associated with human disorders including cancer and cardiovascular disease. The focus of this application is to characterise the role of the ubiquitin protein ligase Nedd4 in vascular development, with the aim of identifying targets to which novel therapeutics for the treatment of blood and lymphatic vascular diseases could be generated.