Role Of Endothelial Vasodilator Mechanisms In Cardiovascular Control During Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$225,500.00
Summary
Cardiovascular diseases such as stroke and heart attack are the greatest killers in developed societies such as Australia. We now know that a number of metabolic disorders, and genetic and lifestyle factors, can increase the likelihood of individuals developing cardiovascular disease later in life, such as obesity, diabetes, and smoking. In many cases, individuals with these risk factors also have high blood pressure, which is a known cause of stroke and heart attack. This seems to be a particul ....Cardiovascular diseases such as stroke and heart attack are the greatest killers in developed societies such as Australia. We now know that a number of metabolic disorders, and genetic and lifestyle factors, can increase the likelihood of individuals developing cardiovascular disease later in life, such as obesity, diabetes, and smoking. In many cases, individuals with these risk factors also have high blood pressure, which is a known cause of stroke and heart attack. This seems to be a particular problem in patients with diabetes, a condition that currently affects around 150 million people worldwide. Indeed, almost 70% of patients that develop diabetes in later life, also develop high blood pressure. The aim of the studies outlined in this application is to increase our understanding of the way diabetes affects blood pressure. High blood pressure often accompanies established diabetes, but we have recent evidence that suggests that a gas (nitric oxide) made by the cells that line blood vessels (endothelial cells) and in nerve cells, protects the cardiovascular system from hypertension during the onset of diabetes. Our experiments will show whether the 'protective' nitric oxide comes from nerves or the endothelial cells, and how it affects various blood pressure control mechanisms in diabetes. Our experiments will also show whether this protective action of nitric oxide is eventually lost as the organ damage that occurs in diabetes proceeds. This information should help in the design of new drug treatments and other therapies aimed at reducing the occurrence of high blood pressure, and hence cardiovascular disease, in diabetes.Read moreRead less
B Cell Activation Generates Antibodies To Promote Vascular And Renal Inflammation, Remodelling And Dysfunction In Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$327,193.00
Summary
Hypertension is a major contributor to chronic cardiovascular and renal diseases, with recent literature suggesting the pathogenesis is similar to that of autoimmune diseases. This fellowship will enhance the current understanding of the pathogenesis of hypertension and the associated inflammation of the kidneys and vasculature. It will also assess the therapeutic potential of drugs that dampen the immune response in several animal models of hypertension.
Prognostic Markers Of Cardiovascular Risk In Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$104,132.00
Summary
One in three Australians are at risk of chronic kidney disease; however, these patients are more likely to die of heart disease. There is a need to identify markers in kidney failure patients to detect heart disease early. Unmasking cardiac risk factors by using change in cardiac biomarkers and echocardiographic parameters with exercise is novel. This will help the physician to diagnose _subclinical� cardiovascular dysfunction early, hence preventing cardiovascular mortality by institution of ap ....One in three Australians are at risk of chronic kidney disease; however, these patients are more likely to die of heart disease. There is a need to identify markers in kidney failure patients to detect heart disease early. Unmasking cardiac risk factors by using change in cardiac biomarkers and echocardiographic parameters with exercise is novel. This will help the physician to diagnose _subclinical� cardiovascular dysfunction early, hence preventing cardiovascular mortality by institution of appropriate therapies.Read moreRead less
Targeting Innate Immunity To Prevent Chronic Dysfunction Of The Transplanted Kidney
Funder
National Health and Medical Research Council
Funding Amount
$497,057.00
Summary
Kidney transplantation is the optimal treatment for patients suffering from end-stage kidney disease. Chronic transplant dysfunction is the major barrier to long-term health after transplantation, and is the subject of this application. Our studies suggest a signaling system activates immunity and leads to chronic transplant dysfunction. We aim to block this signaling system in mouse models to identify clinically applicable treatments to prevent kidney transplant failure.
A Novel And Unique Protein I-body For The Treatment Of Chronic Kidney Disease Through Targeting CXCR4
Funder
National Health and Medical Research Council
Funding Amount
$768,340.00
Summary
Chronic kidney disease (CKD) is a worldwide public health problem, with adverse outcomes of kidney failure, cardiovascular disease, and premature death. Kidney transplantation and dialysis are the only options for the management of CKD, which results in a significant burden on the health system. The central aim of this project is to develop a novel therapeutic strategy to limit/reverse CKD, which will lead to a researcher-industry partnership in discovery of novel therapeutic agent.
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