Regulation Of Vascular Tone By Indoleamine 2,3-dioxygenase
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
As part of their normal function, blood vessels dilate and contract, for example in response to the pulsative force with which our heart pumps the blood around the circulation. Blood vessels produce several different chemicals that cause vessel relaxation, and these vary depending on several factors, such as the blood vessel involved, its diameter and precise location within our body. In addition to responding to the pulsative nature of blood flow, blood vessels also respond to many other condit ....As part of their normal function, blood vessels dilate and contract, for example in response to the pulsative force with which our heart pumps the blood around the circulation. Blood vessels produce several different chemicals that cause vessel relaxation, and these vary depending on several factors, such as the blood vessel involved, its diameter and precise location within our body. In addition to responding to the pulsative nature of blood flow, blood vessels also respond to many other conditions, including certain diseases, so that it is not surprising that many of the commonly used cardiovascular drugs target to change blood vessel tone, either increasing or decreasing blood pressure, depending on the circumstances involved. The present application is based on the discovery, in the mouse, that during a systemic infection a specific protein is induced in the cells that line blood vessels. This protein degrades a certain amino acid into a novel chemical, called kynurenine. We observed that kynurenine has previously unrecognised vessel-relaxing properties. The present project will investigate the importance of kynurenine formation as a novel pathway in the regulation of vascular tone. Mice, in which the activity of the kynurenine-producing protein will be modulated (both up and down) will be used in conjunction with blood pressure and other relevant measurements. In addition, the role of a unique molecule, called superoxide anion radical, in the production of kynurenine by the protein will also be tested. If our results confirm that the protein and kynurenine are indeed involved in regulating vascular tone, our research could have tremendous impact on many aspects of normal physiology as well as cardiovascular diseases that remain the major single cause of death in Australia.Read moreRead less
Does Inhibition Of Myeloperoxidase Attenuate Atherosclerosis?
Funder
National Health and Medical Research Council
Funding Amount
$572,659.00
Summary
This project examines whether inhibition of a protein that produces bleach and is part of the immune system inhibits the stiffening of arteries, i.e. the major cause of cardiovascular disease that leads to heart attack and stroke. The project uses a pharmacological approach, employing a new class of chemical compounds. If successful, the project will contribute to the establishing of a novel therapeutic target to combat cardiovascular disease.
Control Of Cardiac And Skeletal Contractility By Luminal Calcium Store Load In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$415,138.00
Summary
Disorders affecting skeletal muscle and the heart can have life threatening effects and lead to impaired mobility and sudden cardiac death. This project will uncover the mechanisms of disorders which lead to skeletal muscle fatigue, chemotherapy induced toxicity in the heart and heart failure. Understanding these mechanisms may lead to successful gene therapy treatment and to the design of a new range of drug therapies to treat these devastating disorders.
Role Of Microvascular Flowmotion In Skeletal Muscle Glucose Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$596,971.00
Summary
Obesity and type 2 diabetes are nationally and globally reaching epidemic rates. This project investigates the regulation of blood flow within muscle and its impact on metabolism. Outcomes from the study may lead to diagnostic tools and treatments for cardiovascular disease associated with obesity, hypertension and type 2 diabetes.
Identification Of Novel Secretory Factors From The Heart As New Targets For Metabolic Disease
Funder
National Health and Medical Research Council
Funding Amount
$864,012.00
Summary
The incidence of obesity, type 2 diabetes and cardiovascular disease is rising at an alarming rate. The communication between the heart and distal tissues represents an exciting and emerging research area which has the potential to result in the identification of new targets and therapies. Here we will identify novel circulating proteins which could be developed as innovative therapies and ultimately translated into the clinic.
Actions Of The Polyphenol Epigallocatechin 3-gallate On Insulin Sensitivity
Funder
National Health and Medical Research Council
Funding Amount
$409,746.00
Summary
This project will determine whether the bioactive compound in green tea (called EGCG) can reduce insulin resistance by enhancing the ability of insulin to open very small blood vessels (called capillaries) in muscle. Opening more capillaries will help glucose to be stored in muscle, thus alleviating insulin resistance. Findings from these studies may have important impact on the management of insulin resistance and type 2 diabetes.
Mechanisms Of Vascular Dysfunction During Acute And Chronic Hyperglycemia
Funder
National Health and Medical Research Council
Funding Amount
$56,700.00
Summary
Increased consumption of sugary drinks has contributed to an epidemic of obesity and diabetes and consequently cardiovascular disease. For the first time in living memory, this may well lead to declining life-expectancy. My research will examine both the short and long-term impact of sugary drinks on vital blood vessel function. In the process it will develop better methods to monitor blood vessel function and inform public health policy on sugary drinks and preventing cardiovascular disease.
Novel Small Molecule FosB/AP-1 Inhibitors For The Prevention Of Proliferative Vascular Disorders
Funder
National Health and Medical Research Council
Funding Amount
$343,597.00
Summary
This project examines the effect of a novel FosB/AP-1 inhibitor (LK001) on neointima formation after injury in animal models of restenosis, atherosclerosis and abdominal aortic aneurysm, and a human ex vivo model of graft stenosis Given the current prevalence of CVD in Australia and the increasing demographic of susceptible individuals in the ageing population, this project has enormous clinical implications.
RZR-alpha In The Control Of Proliferative Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$521,706.00
Summary
Four million Australians have cardiovascular disease accounting for 35% of all deaths. CVD is the most expensive disease burden and a National Health Priority. Smooth muscle cell growth is a cause of CVD. However, the mechanisms controlling SMC hyperplasia are poorly understood. This project will provide key insights on the role of RZR-alpha in the pathogenesis of blood vessel disease, and develop novel gene-targeting approaches for new opportunities to control complications of CVD.