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
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.
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
New Insights Into The Role Of Renal Endothelial Dysfunction In The Pathogenesis Of Glomerular Injury And Renal Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$577,722.00
Summary
This project will ascertain whether abnormal function of endothelial cells contribute to diabetic and non-diabetic kidney diseases, the leading cause of end-stage kidney disease. The outcome of this study will allow us to reevaluate the role of endothelial cells in kidney scarring, lead us to question our current approaches to the treatment and management of chronic kidney disease and eventually may be helpful for the design of novel therapies to treat chronic kidney diseases.
The Effect Of CPAP On Erectile And Endothelial Dysfunction In Impotent Men With Obstructive Sleep Apnea
Funder
National Health and Medical Research Council
Funding Amount
$609,559.00
Summary
Erectile dysfunction is common in men with obstructive sleep apnea, due to vascular damage, which leads to heart attack. CPAP is the preferred treatment for patients with OSA because of its well-proven ability to decrease sleepiness and improve blood pressure control. This study will establish if CPAP can also improve erectile and vascular endothelial dysfunction. These results will shed light on the mechanisms that underpin the relationship between OSA and Erectile Dysfunction.
NEPHROTOXICITY OF ANGIOTENSIN INHIBITION DURING RENAL DEVELOPMENT
Funder
National Health and Medical Research Council
Funding Amount
$210,990.00
Summary
Renal dysplasia and renal cystic disease remain significant clinical problems in the paediatric population. Initial animal experiments have demonstrated that inhibiting the renal vasoactive peptide angiotensin during development results in a form of medullary cystic disease. The experiments in this project are aimed at understanding the specific roles and interactions that angiotensin plays in renal development, particularly in development of the distal nephron, the vasculature and the renal pel ....Renal dysplasia and renal cystic disease remain significant clinical problems in the paediatric population. Initial animal experiments have demonstrated that inhibiting the renal vasoactive peptide angiotensin during development results in a form of medullary cystic disease. The experiments in this project are aimed at understanding the specific roles and interactions that angiotensin plays in renal development, particularly in development of the distal nephron, the vasculature and the renal pelvis. Importantly the time course of growth and differentiation of these structures varies and the time course of inactivation of angiotensin may result in different malformations. Information from these studies will allow us to understand how clinical problems can arise when angiotensin is absent or other players modify its action. Such situations can arise in humans through sporadic genetic mutations that may well not manifest in widespread clinical abnormalities.Read moreRead less