A Study Of The Origins Of Macrophages In Healthy And Atherosclerotic Vasculature Focusing On A Novel Population Of Resident Adventitial Macrophage Progenitor Cells (AMPCs)
Funder
National Health and Medical Research Council
Funding Amount
$465,345.00
Summary
White blood cells (macrophages) play a key role in the development of atherosclerosis, the underlying cause of most heart attacks and strokes. We have made new discoveries to show that there are stem (progenitor) cells for macrophages that exist within the outer lining of blood vessels. This project will study whether these local progenitor cells, called AMPCs, are a source of macrophages in atherosclerosis and in turn could lead to new treatment approaches for cardiovascular disease.
Targeting Renal And Vascular Inflammation In Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$781,589.00
Summary
Inflammation is a hallmark of high blood pressure (A.K.A. hypertension) and underlies clinical complications of the condition such as kidney failure and blood vessel disease. This project will investigate whether a recently described signaling complex termed the 'inflammasome' is a trigger of inflammation in hypertension in the hope of identifying it as a target for new drugs that are more effective in the treatment of hypertension and its complications.
Regulator Of G Protein Signalling-5 Loss And Gain Of Function In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$625,428.00
Summary
Cancer and cardiovascular diseases are amongst the largest causes of morbidity and mortality in Western populations. We have identified a molecule, called Regulator of G protein signalling 5 (RGS5), which is involved in vessel remodelling in both diseases. This molecule is a prime candidate for drug development. We will study the precise role of RGS5 in sophisticated preclinical models which will create future opportunities for urgent therapy.
Cancer causes significant morbidity and mortality in Australia’s aging population. There is strong evidence that abnormal blood vessels in tumours limit drug access and drive metastases. We have identified a molecule which controls vessel remodelling in tumours. In this proposal we will study mechanisms on how the molecule itself is regulated with the aim to normalize blood vessels for improved therapy.
Molecular Mechanisms In Pregnancy-indcuded Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$649,668.00
Summary
Approximately 5-10% of pregnancies are complicated by hypertension with associated health risks for both mother and child. To keep blood pressure at normal levels during pregnancy requires active regulation, but underlying processes are not yet fully understood. We have identified a molecule which crucially controls blood pressure during pregnancy. In this proposal we will study how the molecule remodels blood vessels in pregnant females to optimize pharmacological intervention and pregnancy out ....Approximately 5-10% of pregnancies are complicated by hypertension with associated health risks for both mother and child. To keep blood pressure at normal levels during pregnancy requires active regulation, but underlying processes are not yet fully understood. We have identified a molecule which crucially controls blood pressure during pregnancy. In this proposal we will study how the molecule remodels blood vessels in pregnant females to optimize pharmacological intervention and pregnancy outcomes in humans.Read moreRead less
Vascular And Neurogenic Determinants Of Hypertension In Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$508,142.00
Summary
You are as old as your arteries, and people with kidney disease have arteries that age fast. They also have overactive sympathetic nerves, and it is not clear if the blood vessels or nerves are responsible for the high blood pressure that puts strain on the heart and other organs of these patients. We will use an animal model to determine if therapy for hypertension reduces the stiffness of blood vessels or elevated nerve activity. Our results will enable better treatments for kidney failure.
The Central Role Of Connective Tissue Growth Factor In Remodelling Of Asthmatic Airways
Funder
National Health and Medical Research Council
Funding Amount
$689,019.00
Summary
In the asthmatic airway an increase in the number of blood vessels can affect an asthmatic's ability to breathe. We have recently found that growth factors which can promote vessel growth are increased in the airways of asthmatics. We want to understand how these growth factors act together to possibly control the blood vessels and how their behaviour is different in the asthmatic airways compared to the nonasthmatic airways.
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 Critical New Signaling Axis In Lymphatic Vascular Angiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$700,784.00
Summary
The lymphatic vasculature is a crucial part of our vascular system required for tissue fluid drainage and maintenance of fluid homeostasis. Lymphatic vessels play major roles in vascular pathologies and in the spread of solid tumours during cancer progression. We have discovered a new molecular regulator controlling the formation of lymphatic vessels. This project will determine the signalling pathway employed by this new regulator and potential for future therapeutic applications.
Impaired Respiratory Tolerance In Obesity - The Link With Asthma?
Funder
National Health and Medical Research Council
Funding Amount
$667,294.00
Summary
Australia has one of the highest obesity rates in the world, placing a major strain on health budgets. Obesity increases the risk of numerous diseases, including asthma. Asthma is prevented in healthy people by the immune system. This project will investigate whether obesity-related dietary factors and/or gut microbes impair this immune-mediated mechanism. Outcomes will increase understanding of the effects of diet and obesity on asthma development, and lead to novel asthma therapies.