Understanding How GATA2 Controls Lymphatic Vessel Valve Development
Funder
National Health and Medical Research Council
Funding Amount
$697,942.00
Summary
Mutations in the GATA2 gene cause human lymphoedema as a result of the crucial role that GATA2 plays in controlling the expression of genes important for building functional lymphatic vessels. Here we aim to gain a complete picture of the cellular and molecular events that are controlled by GATA2 in lymphatic vessels and in particular, in lymphatic vessel valves.
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.
Bioengineering Endovascular Prostheses With Proactive Biocompatibility
Funder
National Health and Medical Research Council
Funding Amount
$627,950.00
Summary
Metallic cardiovascular implants, such as stents, used in the treatment of heart disease are not compatible with blood. They cause inflammation at the site of implantation and increase the risk of blood clots forming. We have developed a unique method of binding bioactive protein layers to the surface of metal alloys, and shown a significant improvement in their compatibility. Stents coated using our technology stand to dramatically improve the treatment of cardiovascular disease.
Development Of Endovascular Stents With Proactive Biocompatibility
Funder
National Health and Medical Research Council
Funding Amount
$428,470.00
Summary
Metallic cardiovascular implants, such as stents, used in the treatment of heart disease are not compatible with blood. They cause inflammation at the site of implantation and increase the risk of blood clots forming. We have developed a unique method of binding bioactive protein layers to the surface of metal alloys, and shown a significant improvement in their compatibility. Stents coated using our technology stand to dramatically improve the treatment of cardiovascular disease.
Role For Sphingosine Kinase-1 In Endothelial Progenitor Cell Survival And Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$294,205.00
Summary
Lay description: Collectively, diseases of the vascular system contribute immensely to the burden of health care in Australia. Notably, abnormal blood vessel formation and function (angiogenesis) has been identified as a major cause or contributor to the vascular complications associated with inflammation, cancer, rheumatoid arthritis and diabetes. Endothelial cells are one of the principle cells of blood vessels forming a barrier between the blood and tissues. This project aims to understand th ....Lay description: Collectively, diseases of the vascular system contribute immensely to the burden of health care in Australia. Notably, abnormal blood vessel formation and function (angiogenesis) has been identified as a major cause or contributor to the vascular complications associated with inflammation, cancer, rheumatoid arthritis and diabetes. Endothelial cells are one of the principle cells of blood vessels forming a barrier between the blood and tissues. This project aims to understand the process whereby mature endothelial cells are formed and how replacement of damaged endothelial cells is normally achieved. Stem cell therapy is considered the new frontier for the treatment of many diseases. Understanding how endothelial progenitor cells differentiate to mature endothelial cells and the signals which operate inside the cell may allow therapeutic manipulation of key target moecules in order to limit or control inflammation, tumourigenesis, rheumatoid arthritis and diabetic retinopathy. Our results suggest that one target maybe the enzyme sphingosine kinase.Read moreRead less
Microvascular Complications Of Diabetes - Potential Role Of Regenerative Therapies
Funder
National Health and Medical Research Council
Funding Amount
$32,003.00
Summary
The global burden of diabetes is projected to reach more than 366 million by 2025. According to the AusDiab 2005 study, each year 0.8% of Australians develop diabetes. Diabetes is the leading cause of end-stage kidney disease in Australia. Current treatments slow damage to the kidney, but do not reverse kidney damage. We will explore the potential for adult progenitor cells (endothelial progenitor cells) to reverse damage to the kidney and restore its function.
The health benefits of consuming fruits and vegetables can in part be attributed to their high content of polyphenolic compounds such as flavonoids. These substances can improve functioning of blood vessels and have the potential to reduce the risk of heart disease. This project will examine one of the most common flavonoids in the diet to try and understand how it works and better understand the protective effects.
Defining The Molecular Events That Initiate The Genesis Of Lymphatic Vessels.
Funder
National Health and Medical Research Council
Funding Amount
$555,325.00
Summary
Lymphatic vessels are a vital component of the cardiovascular system. Abnormalities in the growth and development of lymphatic vessels are associated with human disorders including lymphoedema, cancer and inflammatory diseases. The focus of this application is to determine the molecular events that initiate the construction of lymphatic vessels, with the aim of identifying targets to which novel therapeutics for the treatment of lymphatic vascular diseases could be generated.
Anti-atherosclerotic Effects Of Angiotensin Fragments & Non-AT1 Receptors: Validation As Innovative Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$512,065.00
Summary
In Australia the largest cause of death is coronary heart disease (CHD) leading to heart attacks or stroke and claiming a staggering 28,000 lives a year. Atherosclerosis is one of the leading causes of cardiovascular disease, with diseased vessels not able to fully dilate and the plaque that has built up inside these vessels impeding blood flow and possibly rupturing, resulting in heart attacks and stroke. One of the major players in the development and progression of atherosclerosis is the horm ....In Australia the largest cause of death is coronary heart disease (CHD) leading to heart attacks or stroke and claiming a staggering 28,000 lives a year. Atherosclerosis is one of the leading causes of cardiovascular disease, with diseased vessels not able to fully dilate and the plaque that has built up inside these vessels impeding blood flow and possibly rupturing, resulting in heart attacks and stroke. One of the major players in the development and progression of atherosclerosis is the hormone, angiotensin II. Angiotensin II has been found to trigger many factors that cause thickening of the vessel wall, inflammation and imbalances in vasodilator capacity (e.g. oxidative stress and endothelial dysfunction), all of which contribute to atherosclerosis. Clinical trials with drugs that inhibit the formation of angiotensin II (ACE inhibitors), or block the action of angiotensin II (angiotensin receptor antagonists), have demonstrated a significant decrease in mortality in patients with high risk for cardiovascular disease. However their mechanism(s) of action are not fully understood as the circulating levels of shorter fragments of angiotensin II (such as Ang IV and Ang (1-7)) are raised in the blood when these drugs are used and may contribute to the protective effects of these drugs. Importantly, we have found that both Ang IV and Ang (1-7) have protective effects in atherosclerotic blood vessels. Therefore, we hypothesise that fragments of angiotensin II (such as Ang IV and others) exert anti-atherogenic effects via distinct binding sites that oppose the effects caused by angiotensin II, and that these may be partly responsible for the cardio-protective effects of the ACE inhibitors and angiotensin receptor antagonists. Thus, information gained in our study will be useful in directing future prescription practices in clinical management of CHD and stroke, and for designing new therapeutic compounds for the management of atherosclerosis.Read moreRead less
Preventing Stroke From Arteriovenous Malformations Using Precision Thrombosis
Funder
National Health and Medical Research Council
Funding Amount
$993,866.00
Summary
Brain arteriovenous malformations are rupture-prone blood vessels that cause stroke in children and young adults. One third of patients have no current treatment options. We aim to develop new medicines that cause blockage of the abnormal vessels, thus preventing them from bleeding and causing stroke. Focused radiation is used to produce molecular changes in the abnormal vessels; these molecules are then the target for the new medicines. We will develop several new drugs for clinical testing.