Potential Novel Pharmacological Strategies To Prevent Atherosclerotic Plaque Rupture
Funder
National Health and Medical Research Council
Funding Amount
$1,584,568.00
Summary
Most heart attacks are the consequence of the acute rupture of plaques in arteries that supply our heart with oxygen and nutrients. Current standard tests cannot distinguish plaques that likely rupture from plaques that do not rupture. Similarly, little is known about the processes that determine whether a plaque is vulnerable to rupture or stable. The current project examines the involvement of two processes - either alone or in combination - in determining plaque stability/vulnerability.
Oxidative Processes In Vascular Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$851,980.00
Summary
The process that turns cut fruit brown when it is exposed to air is thought to cause disease of our blood vessels and heart as we age. Despite what we first thought, 'blocking' this oxidation process with antioxidant supplements does not lower heart disease. This is because oxidation not only causes harm but also is useful and essential for normal body function. Our research program aims to show which oxidative processes are needed for blood vessel health or cause vessel disease.
NOX Isoforms In Diabetes Associated Vascular Injury: Implications For Therapeutic Strategies
Funder
National Health and Medical Research Council
Funding Amount
$441,511.00
Summary
These studies will investigate the role of oxidative stress and enzymes involved in oxidative stress production in diabetes associated blood vessel injury and kidney damage, leading to heart attacks, stroke and kidney failure. We will use unique knockout animal models and novel drug treatments. Ultimately, we aim to develop novel treatments to better treat and prevent diabetes related complications.
Fibrosis is a common feature of many forms of heart disease. Despite the recognised central role of reactive oxygen species (ROS) in cardiac fibrosis, antioxidant approaches have failed in clinical trials. We have discovered a new mechanism for ROS-mediated fibrosis that is depleted in human heart failure, and will test an innovative therapeutic approach that is imminently translatable given the development by members of our team of a specific peptide blocker effective in blocking this pathway.
From Fundamental Mechanistic Discoveries To Strategic Methods For Early Detection And Treatment Of Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$412,419.00
Summary
I am an interventional cardiologist whose research program spans from biomedical discovery, to new markers of early cardiovascular disease and clinical trials of new therapy. We are particularly focused on novel strategies to help patients who suffer from heart attack despite having no standard risk factors. I lead a team of cross-disciplinary researchers. A Practitioner Fellowship will help me to achieve international impact against the leading cause of death and disability in our community.
Studies Into Myeloperoxidase-Induced Cardiovascular Disease And Its Treatment
Funder
National Health and Medical Research Council
Funding Amount
$924,596.00
Summary
During cardiovascular disease an inflammatory protein called myeloperoxidase (MPO) becomes abnormally released into the circulating blood and is transported into diseased blood vessels. Our studies show for the first time that increasing circulating levels of MPO promotes both atherosclerosis and aortic aneurysm. This project will study how MPO promotes inflammatory artery disease and test new drugs for their ability to inhibit this damaging protein and protect against cardiovascular disease.
Oxidative Regulation Of The Na Pump- A New Player In Vascular Function In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$504,427.00
Summary
Oxidative stress is a major player in hypertension, atherosclerosis, diabetes and ageing, but we have struggled to develop a therapy to successfully combat in heart and vascular cells in large clinical trials. We have discovered a new role for membrane protein FXYD1, to protect key heart and vascular proteins from functional impairment secondary to oxidative stress. We will investigate its role in protecting against vascular disease, and test novel therapies based on this endogenous protector.
Defining The Roles Of NADPH Oxidases In Vascular Remodelling And Arterial Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$401,523.00
Summary
Hypertension (high blood pressure) is a major risk factor for cardiovascular diseases such as heart attacks, heart failure and stroke - the major causes of death world-wide and a huge burden on the Australian health care budget. Oxidative stress, resulting from an imbalance in the production and removal of toxic molecules called free radicals within the blood vessel wall, is a key player in the initiation and progression of these disorders. In the early stages of hypertension, production of free ....Hypertension (high blood pressure) is a major risk factor for cardiovascular diseases such as heart attacks, heart failure and stroke - the major causes of death world-wide and a huge burden on the Australian health care budget. Oxidative stress, resulting from an imbalance in the production and removal of toxic molecules called free radicals within the blood vessel wall, is a key player in the initiation and progression of these disorders. In the early stages of hypertension, production of free radicals only just outweighs their removal, resulting in a mild oxidative stress. However, this is enough to trigger a cascade of downstream events leading to activation of other, normally dormant, free radical generating systems. At these excessive levels, free radicals attack the cells of the artery wall leading to blood vessel dysfunction and ultimately cardiovascular disease. A major source of free radicals in the blood vessel wall are a family of enzymes called NADPH oxidases. It is our hypothesis that upregulation of onr of these enzymes in the early stages of hypertension is the initial trigger for many of the downstream effects that ultimately lead to cardiovascular disease. Our group is uniquely poised to test this hypothesis as we are the only laboratory in the world with access to three different strains of genetically modified mice, each lacking one of the three known isoforms of NADPH oxidase. Identification of the specific isoform of NADPH oxidase involved in free radical production in blood vessels is a critical first step in developing drugs that block vascular free radical production and so remove the molecular link between hypertension and major cardiovascular events.Read moreRead less