Targeting PI3K-regulated MicroRNAs To Treat Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$532,593.00
Summary
Current therapeutics largely delay heart failure progression rather than regressing it. New therapeutic strategies with the capability of improving function of the failing heart are thus greatly needed. The primary goal of this study is to determine whether novel regulatory genes can enhance cardiac function in a setting of heart failure. Ultimately, technologies that target these genes may lead to innovative pharmacotherapies in the clinical management of heart failure.
IDENTIFICATION OF BRAIN NEURONS INVOLVED IN THE CARDIOVASCULAR RESPONSE TO FEAR AND FLIGHT
Funder
National Health and Medical Research Council
Funding Amount
$400,247.00
Summary
The circulatory system of the body acts in concert with the respiratory system to distribute oxygenated blood to the brain and other organs and tissues of the body. Control of blood pressure and heart rate is achieved largely through the actions of the central nervous system on effector organs and tissues such as the heart and blood vessels. This control is exerted through the actions of nerves in the body which affect the rate and force of contraction of the heart and the diameter of blood vess ....The circulatory system of the body acts in concert with the respiratory system to distribute oxygenated blood to the brain and other organs and tissues of the body. Control of blood pressure and heart rate is achieved largely through the actions of the central nervous system on effector organs and tissues such as the heart and blood vessels. This control is exerted through the actions of nerves in the body which affect the rate and force of contraction of the heart and the diameter of blood vessels which restrict the flow of blood to the tissues. These nerves, in turn, are under the control of brain cells or neurons which are located in the brainstem. Blood pressure-controlling neurons, acting upon information they receive from pressure sensors in the major blood vessels in the chest cavity, can alter their activity so that blood pressure is maintained within normal limits. Our laboratory has been examining the properties of these blood pressure-controlling neurons by recording their minute electrical discharges and by studying other brain regions which are able to influence them. In this study, we will use newly-developed procedures which will allow us to identify the precise locations of these neurons in the brain, to study which neurotransmitters (chemicals released by neurons which are used to communicate with other neurons) they use, as well as to identify other regions of the brain they connect with and influence. The major significance of this work will be that new brain circuits which transmit information about the status of the cardiovascular system to other areas of the brain will be identified. Our understanding of, and the development of new treatments for, cardiovascular diseases such as high blood pressure and heart failure are critically dependent on advancing our understanding of the nervous system.Read moreRead less
A Randomised Controlled Trial Of A Nurse-led Intervention For Less Chronic Heart Failure: The NIL-CHF Study
Funder
National Health and Medical Research Council
Funding Amount
$1,166,160.00
Summary
The overall aim of the unique NIL-CHF Study is to examine the benefits of applying a specialist nurse-led, home and clinic-based intervention to optimise the care of recently discharged hospital patients with heart disease. Involving 950 patients, it will explore whether more flexible and individualised care to apply the best possible medical treatments is able to PREVENT the most deadly and disabling form of heart disease (chronic heart failure - CHF) and save money in the process.
Circulating Low -molecular Weight AGEs In The Development And Progression Of Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$297,523.00
Summary
High levels of sugars seen in patients with diabetes leads to damage of many organs including the heart, the eyes and the kidneys. These high sugars cause damage through a number of mechanisms, one being the formation of advanced glycation end products or AGEs, formed by the irreversible reaction between proteins and glucose. This reaction leads to a change in the shape and function of AGE-modified molecules that progressively contributes to organ damage. AGEs also bind and activate specific rec ....High levels of sugars seen in patients with diabetes leads to damage of many organs including the heart, the eyes and the kidneys. These high sugars cause damage through a number of mechanisms, one being the formation of advanced glycation end products or AGEs, formed by the irreversible reaction between proteins and glucose. This reaction leads to a change in the shape and function of AGE-modified molecules that progressively contributes to organ damage. AGEs also bind and activate specific receptors that promote the damage and scarring of tissue. Where the glucose concentration is high, AGEs accumulate much more quickly. This is one reason why patients with good sugar control do better than those who are unable to control their blood sugars. The importance of this AGE pathway is illustrated by the fact that blocking the formation of AGEs is able to prevent kidney damage in animals with diabetes. In addition, exposure to AGEs can cause diabetes-like changes in the absence of high sugars. Our laboratory is a world leader in the study of the advanced glycation and methods blocking this process. The research proposed will investigate circulating levels of AGEs in experimental animals and patients with diabetes, and correlate them with the development and progression of complications of diabetesRead moreRead less
Enhancing Erythropoietin Therapy In Ischaemia-reperfusion Injury Of Heart And Kidney
Funder
National Health and Medical Research Council
Funding Amount
$361,021.00
Summary
Heart attacks and kidney disease from a lack of blood flow are common causes of morbidity and have poor treatment options. Erythropoietin (epo) is a useful new treatment, but there remain some caveats to its use in humans: eg. it may cause excessive scarring during repair. Use of epo with an anti-inflammatory drug may decrease scarring and provide benefit to long-term health. We plan to carefully define the biomolecular pathways of injury and repair, to better plan this therapy for human use.
Mechanisms Of Infection Triggered Renal Vasculitis
Funder
National Health and Medical Research Council
Funding Amount
$413,900.00
Summary
Kidney disease, including glomerulonephritis, is an important cause of ill-health in Australia. Some forms of kidney inflammation are linked to infection, but we don�t understand why. This project explores products from bacteria, particularly S.aureus, to work out how bacterial infection affects a form of kidney inflammation - ANCA-associated glomerulonephritis. It will establish how infection related signals activate local and immune cells, and define links between infection and the disease.
Immunoregulation In The Pathogenesis And Therapy Of Autoimmune Anti Myeloperoxidase Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$283,880.00
Summary
Glomerulonephritis (GN) is a major health burden and crescentic GN is the most severe form. Most patients have autoantibodies to their own white blood cell ANCA, causing the disease. This study will use a mouse model of ANCA associated autoimmunity causing crescentic GN to define the normal mechanisms preventing the development of this disease (immunoregulation) and test the potential of new cell based therapies to prevent and treat the disease.
The Role Of IL-18 In Proliferative And Crescentic Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$56,177.00
Summary
Inflammation of the small filters with the kidneys, known as glomerulonephritis, is the commonest cause of kidney failure in Australia. People whose kidneys have failed need either kidney dialysis or a kidney transplant. Our understanding of the immune events that cause glomerulonephritis is patchy. However, it is known that T cells are the directors of immune responses in the body and direct the immune response in glomerulonephritis. Chemical messengers known as cytokines direct the way T cells ....Inflammation of the small filters with the kidneys, known as glomerulonephritis, is the commonest cause of kidney failure in Australia. People whose kidneys have failed need either kidney dialysis or a kidney transplant. Our understanding of the immune events that cause glomerulonephritis is patchy. However, it is known that T cells are the directors of immune responses in the body and direct the immune response in glomerulonephritis. Chemical messengers known as cytokines direct the way T cells behave. One of these cytokines, known as interleukin-18, has been shown to stimulate T cells and other immune cells to induce inflammation that is helpful when the body is fighting infection but is harmful in immune diseases. This project will determine the role of interleukin-18 in glomerulonephritis by studying the way it talks to T cells and the mechanisms by which it incites inflammation in the kidney. Mice with glomerulonephritis will be treated by blocking the actions of interleukin-18 to discover whether interleukin-18 produced by the animal is important in kidney damage induced by glomerulonephritis, to understand the way in which this cytokine works and to assess whether blocking interleukin-18 could be a useful treatment for glomerulonephritis in humans. Current treatments for glomerulonephritis are often ineffective and have unwanted side effects. Knowledge of the way interleukin-18 participates in the immune response in glomerulonephritis may lead directly or indirectly to more effective and more targeted treatments for different forms of glomerulonephritis.Read moreRead less
Mechanisms Of Disease In Humans With MPO-ANCA Associated Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
Glomerulonephritis (GN) is a major health burden and crescentic GN is the most severe form. Most patients have autoantibodies to their own white blood cell ANCA, causing the disease. This study plans to assess immune cells and kidney biopsies from patients with anti-MPO GN to define more precisely the immune mechanisms causing disease.
Urotensin-II In Human Heart: Investigation Of Mechanisms Involved In Cardiac Function
Funder
National Health and Medical Research Council
Funding Amount
$255,990.00
Summary
The normal function of the body is maintained by naturally occurring compounds. Some for example affect the heart, fine tuning it to make it beat faster or slower, or beat with greater or less force when required in different situations in health and disease. We were the first to show just recently that a small protein which occurs naturally in the body, called urotensin-II can affect the way the heart beats. We showed that extremely tiny amounts increase the force of the heart beat. Our finding ....The normal function of the body is maintained by naturally occurring compounds. Some for example affect the heart, fine tuning it to make it beat faster or slower, or beat with greater or less force when required in different situations in health and disease. We were the first to show just recently that a small protein which occurs naturally in the body, called urotensin-II can affect the way the heart beats. We showed that extremely tiny amounts increase the force of the heart beat. Our findings indicate that urotensin-II is the most potent heart stimulator identified to date. In patients with heart failure, short term stimulation of heart contraction is beneficial, supplying the heart and other organs with vital oxygen and nutrients. However, in the long term excessive stimulation causes worsening of the patients condition. Very little is currently known about the way in which urotensin-II alters heart function. The goal of our study is to understand the mechanism involved in urotensin-II mediated effects on the heart. This will involve identifying the location of urotensin-II and its receptors in the heart, and determining what signalling changes occur after the interaction of urotensin-II with its receptors. Urotensin-II must first be cleaved from a larger drug. We will determine where in the heart this cleavage occurs and whether the process is crucial to the ability of urotensin-II to stimulate contraction of the heart. Since stimulators of heart contraction are detrimental to patients with heart failure in the long term, we will determine whether these patients have more urotensin-II in their blood than patients who do not have heart failure. If the levels of urotensin-II are higher in heart failure patients, it may indicate a need to interfere with the interaction of urotensin-II with its receptors.Read moreRead less