Optimising Efficacy Of A Peptide Derived Against The Alpha-interacting Domain Of The L-type Calcium Channel In Reduction Of Ischemia-reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$405,063.00
Summary
A heart attack is associated with an increase in free radicals and calcium in heart muscle cells. The function of the L-type calcium channel, a protein responsible for calcium entry into cells, is altered by free radicals and this contributes to the development of heart disease. We now have considerable proof of concept that a peptide derived against the L-type calcium channel can decrease heart injury. We will optimise efficacy and delivery of the peptide to prevent heart failure.
Catheter Based Renal Denervation To Improve Outcomes In Congestive Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$619,194.00
Summary
In heart failure there is a large increase in sympathetic nerve activity that is detrimental to patient outcome, but the factors causing this increased activity are not well defined. There is evidence that renal nerves play a significant role. A novel catheter based technique allows silencing of these nerves. We will test whether this novel technique has the potential to improve the outcomes for patients with heart failure.
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.
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
Role Of Sympathetic Nervous System In The Development Of Early Organ Damage In Obesity:an Emerging Target For Therapy
Funder
National Health and Medical Research Council
Funding Amount
$544,534.00
Summary
Young people with obesity often have no signs of cardiovascular disease but their organs, such as the heart, the kidneys and the blood vessels present early evidence of damage that can, in time, progress to confer cardiovascular risk. This study will look at the potential beneficial effect of a drug, by itself or in association with a low calorie diet, in reversing the progression of organ damage in young obese subjects.
Understanding The Cardio-protective Actions Of The AT2R In Females: Shifting Gears Between AT1 And AT2 Receptor Balance Of Function With Relaxin.
Funder
National Health and Medical Research Council
Funding Amount
$1,049,288.00
Summary
Women are protected from cardiovascular disease as compared to age-matched men, an effect lost with age. Understanding protective factors that act in females could be used to treat hypertension, heart failure and stroke in males at all ages, and maintain protection in elderly women. Our studies aim to determine if relaxin, an ovarian hormone, can promote cardiovascular health in women.
Heart attacks remain a major cause of morbidity and mortality. I am an interventional cardiologist who heads an expanding basic and translational science laboratory (Cardiac Oxidative Signalling) at the Kolling Institute and who plays a leading role in clinical cardiovascular research at Royal North Shore Hospital. My vision is to translate fundamental discoveries in our Laboratory to new therapies and methods of risk stratification to improve immediate and long term outcomes of patients sufferi ....Heart attacks remain a major cause of morbidity and mortality. I am an interventional cardiologist who heads an expanding basic and translational science laboratory (Cardiac Oxidative Signalling) at the Kolling Institute and who plays a leading role in clinical cardiovascular research at Royal North Shore Hospital. My vision is to translate fundamental discoveries in our Laboratory to new therapies and methods of risk stratification to improve immediate and long term outcomes of patients suffering heart attack.Read moreRead less
NADPH Oxidase And Brain Repair After Ischaemic Stroke
Funder
National Health and Medical Research Council
Funding Amount
$641,877.00
Summary
Stroke is the third most common cause of death, results in considerable suffering and presents an enormous cost to health budgets. New research suggests that the injured brain can be stimulated to improve function. Generation of free radicals in the brain in the weeks after stroke may be important in long term recovery by promoting new blood vessel formation to suport brain repair. In this project we seek to identify how, when and where new blood vessels assist stem cell mediated repair.
Reversing Oxidative Inhibition Of The Na-K Pump By Beta3 Adrenergic Agonists: Implications For Heart Failure Therapy
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
Heart failure is a debilitating condition characterised by a decreased heart pump function. Raised Na+ levels and increased oxidative stress in cardiac cells are important in its causation. While traditional antioxidants are not useful in treatment, we have found that a group of drugs designed to induce weight loss can reverse oxidative inhibition of the mechanism that pumps Na+ out of heart cells. The effect of these drugs on the Na+ pumping mechanism and heart failure will be examined.
Role Of Myeloperoxidase In Endothelial Barrier Dysfunction During Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$302,123.00
Summary
The release of the enzyme myeloperoxidase (MPO) within blood vessels is thought to affect their ‘leakiness’ during periods of inflammation, leading to fluid associated swelling (oedema). We propose that MPO produces oxidant chemicals that increase blood vessel leakage. The aim of our work is to study how these chemicals increase vascular leakage by studying the biochemical pathways involved. These studies could lead to new intervention strategies targeting MPO to reduce excessive tissue oedema.