Endothelial Development From Pluripotent Stem Cells As A Means To Study Pathology In Pulmonary Artery Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$613,311.00
Summary
Pulmonary artery hypertension (PAH) is a fatal disease primarily affecting young adults. It is caused by a defect in cells that form the vessel that carries blood from the heart to the lungs. We will use stem cells made from the skin of PAH patients to examine why the blood vessel cells from these patients fail to function normally.
Mechanisms And Therapies In Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$8,360,700.00
Summary
Cardiovascular disease (CVD) claims 1 person every 10 min in Australia and causes 1 in 3 deaths worldwide. The molecular and cellular processes underlying atherosclerosis, vascular injury and thrombosis are highly complex and not well understood. A multifaceted approach is needed to effectively address these key challenges. This Program brings together world experts in these areas to interrogate gaps in our basic understanding of CVD, and to develop novel therapies for CVD patients by exploiting ....Cardiovascular disease (CVD) claims 1 person every 10 min in Australia and causes 1 in 3 deaths worldwide. The molecular and cellular processes underlying atherosclerosis, vascular injury and thrombosis are highly complex and not well understood. A multifaceted approach is needed to effectively address these key challenges. This Program brings together world experts in these areas to interrogate gaps in our basic understanding of CVD, and to develop novel therapies for CVD patients by exploiting new knowledge through integrated research.Read moreRead less
Suppression Of NADPH Oxidase-derived Oxidative Stress By Anti-sense Probes And HDL In Human Vascular Endothelium
Funder
National Health and Medical Research Council
Funding Amount
$455,250.00
Summary
In Australia, coronary heart disease (CHD) causing heart attacks remains the largest cause of death, claiming a staggering 28,000 lives a year. Oxidative stress, resulting from increased production of oxygen free radicals in arteries, is an important cause of CHD, heart attacks and strokes. We seek to understand how such oxyradicals are produced in the key cells that form the lining of all arteries, known as the vascular endothelium. By using novel DNA-type molecules (known as anti-sense) develo ....In Australia, coronary heart disease (CHD) causing heart attacks remains the largest cause of death, claiming a staggering 28,000 lives a year. Oxidative stress, resulting from increased production of oxygen free radicals in arteries, is an important cause of CHD, heart attacks and strokes. We seek to understand how such oxyradicals are produced in the key cells that form the lining of all arteries, known as the vascular endothelium. By using novel DNA-type molecules (known as anti-sense) developed in our laboratory, which block a particular gene causing oxidative stress, we will determine whether this gene is responsible for the formation of oxyradicals in human and mouse cells grown in culture. In addition, we will explore whether this gene is turned on by factors known to be involved in CHD. Finally, we will also investigate whether the good cholesterol known as HDL can act to prevent oxidative stress in human cells, as we discovered it appears to do in living arteries in vivo. If we find it has the same protective effect in endothelium, we will determine how it does this, and which component proteins of the HDL particle are important. This might suggest new treatments to prevent acute events leading to heart attack and stroke, and possibly new applications where damage appears to result from acute oxidative stress, such as in the brain soon after a stroke has occurred. We also have a plan to develop antisense drugs that will target the important gene specifically in the affected endothelium. In addition, we have other specific new drugs that will block this system in arteries. Simultaneously we will be testing the role of this gene in mouse and rabbit models of artery disease, for both our types of drugs might provide valuable new therapeutic agents to target the underlying cause of CHD and not just its symptoms as current drugs do.Read moreRead less
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
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.
Local Sleep In The Awake Brain: An Underlying Cause Of Neurobehavioural Deficits In Sleep Apnea?
Funder
National Health and Medical Research Council
Funding Amount
$582,330.00
Summary
Obstructive sleep apnea (OSA) is a common sleep disorder which significantly impacts daytime functioning leading to excessive sleepiness, and problems with attention and thinking. Currently, the causes for cognitive impairment in OSA (including attentional lapses and performance deficits) are poorly understood. In the awake state, groups of neurons can briefly go “offline” as they do in sleep. These periods of “local sleep” may explain impaired task performance in OSA.
Transdermal Testosterone Therapy: A Potential Treatment For Selective Serotonin Reuptake Inhibitor (SSRI)-associated Sexual Dysfunction In Women
Funder
National Health and Medical Research Council
Funding Amount
$241,351.00
Summary
Female sexual dysfunction (FSD) is frequently reported with selective serotonin reuptake inhibitor (SSRI) therapy and venlafaxine, these being the most common antidepressants used by Australian women. We have shown that testosterone therapy significantly improves sexual function in women with FSD. However SSRI-users have been excluded from these past studies. The aim of this study is to assess the efficacy of transdermal testosterone therapy for treatment of sexual dysfunction associated with SS ....Female sexual dysfunction (FSD) is frequently reported with selective serotonin reuptake inhibitor (SSRI) therapy and venlafaxine, these being the most common antidepressants used by Australian women. We have shown that testosterone therapy significantly improves sexual function in women with FSD. However SSRI-users have been excluded from these past studies. The aim of this study is to assess the efficacy of transdermal testosterone therapy for treatment of sexual dysfunction associated with SSRI therapy.Read moreRead less
Imaging Neutrophil And Endothelial Function In Acute Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$545,517.00
Summary
The glomerulus is a group of small blood vessels which form the filtering component of the kidney. In many diseases, it can be the target of an inappropriate inflammatory response during which white blood cells accumulate in the glomerular blood vessels and cause damage. In this project, we will visualise the blood vessel lining of the glomerulus in order to understand how white blood cells damage this region and cause leakage of protein leak into the urine.
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.
Deciphering The Transcriptional Program That Instructs Lymphatic Endothelial Cell Fate.
Funder
National Health and Medical Research Council
Funding Amount
$541,950.00
Summary
Lymphatic vessels are essential to maintain fluid balance in most tissues of the human body. Further the lymphatic vasculature plays a central role during cancer and contributes to tumour metastasis. Despite this integral function in health and disease little is known about the molecular programs that coordinate gene expression to build a functional vasculature. This research project will address this gap in our knowledge and will open up new therapeutic avenues for lymphatic vascular disorders