A Program Of Research Addressing The Transition From Health To Advanced Cardiovascular Disease.
Funder
National Health and Medical Research Council
Funding Amount
$13,017,057.00
Summary
Cardiovascular disease (CVD) is the major cause of death and disability in Australia and worldwide. This burden will increase without new knowledge. We will address knowledge gaps that delay more effective prevention and control. Our team has a strong track record of influencing clinical practice of CVD prevention, treatment and technology transfer. For many, the first indication of a heart problem is sudden heart attack or death. By understanding mechanisms we aim to develop new tests and treat ....Cardiovascular disease (CVD) is the major cause of death and disability in Australia and worldwide. This burden will increase without new knowledge. We will address knowledge gaps that delay more effective prevention and control. Our team has a strong track record of influencing clinical practice of CVD prevention, treatment and technology transfer. For many, the first indication of a heart problem is sudden heart attack or death. By understanding mechanisms we aim to develop new tests and treatments that prevent heart attack, heart failure and other serious consequences of atherosclerosis.Read moreRead less
Anti-atherosclerotic Effects Of Angiotensin Fragments & Non-AT1 Receptors: Validation As Innovative Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$512,065.00
Summary
In Australia the largest cause of death is coronary heart disease (CHD) leading to heart attacks or stroke and claiming a staggering 28,000 lives a year. Atherosclerosis is one of the leading causes of cardiovascular disease, with diseased vessels not able to fully dilate and the plaque that has built up inside these vessels impeding blood flow and possibly rupturing, resulting in heart attacks and stroke. One of the major players in the development and progression of atherosclerosis is the horm ....In Australia the largest cause of death is coronary heart disease (CHD) leading to heart attacks or stroke and claiming a staggering 28,000 lives a year. Atherosclerosis is one of the leading causes of cardiovascular disease, with diseased vessels not able to fully dilate and the plaque that has built up inside these vessels impeding blood flow and possibly rupturing, resulting in heart attacks and stroke. One of the major players in the development and progression of atherosclerosis is the hormone, angiotensin II. Angiotensin II has been found to trigger many factors that cause thickening of the vessel wall, inflammation and imbalances in vasodilator capacity (e.g. oxidative stress and endothelial dysfunction), all of which contribute to atherosclerosis. Clinical trials with drugs that inhibit the formation of angiotensin II (ACE inhibitors), or block the action of angiotensin II (angiotensin receptor antagonists), have demonstrated a significant decrease in mortality in patients with high risk for cardiovascular disease. However their mechanism(s) of action are not fully understood as the circulating levels of shorter fragments of angiotensin II (such as Ang IV and Ang (1-7)) are raised in the blood when these drugs are used and may contribute to the protective effects of these drugs. Importantly, we have found that both Ang IV and Ang (1-7) have protective effects in atherosclerotic blood vessels. Therefore, we hypothesise that fragments of angiotensin II (such as Ang IV and others) exert anti-atherogenic effects via distinct binding sites that oppose the effects caused by angiotensin II, and that these may be partly responsible for the cardio-protective effects of the ACE inhibitors and angiotensin receptor antagonists. Thus, information gained in our study will be useful in directing future prescription practices in clinical management of CHD and stroke, and for designing new therapeutic compounds for the management of atherosclerosis.Read moreRead less
The Effect Of CPAP On Erectile And Endothelial Dysfunction In Impotent Men With Obstructive Sleep Apnea
Funder
National Health and Medical Research Council
Funding Amount
$609,559.00
Summary
Erectile dysfunction is common in men with obstructive sleep apnea, due to vascular damage, which leads to heart attack. CPAP is the preferred treatment for patients with OSA because of its well-proven ability to decrease sleepiness and improve blood pressure control. This study will establish if CPAP can also improve erectile and vascular endothelial dysfunction. These results will shed light on the mechanisms that underpin the relationship between OSA and Erectile Dysfunction.
Understanding Local And Regional Determinants Of EDHF And NO Dysfunction In Resistance Arteries In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$771,295.00
Summary
Diabetes is a serious and increasing health burden worldwide. Most of the sickness and death associated is due to complications arising in the blood vessels. The inner lining of blood vessels in small arteries uses several different mechanisms to ensure proper blood flow, and in diabetes these are impaired. This study will reveal the cellular mechanisms involved and identify pathways for therapeutic intervention to alleviate the debilitating effects of small artery disease.
Normal organ development and many disease processes, such as cancer and tissue damage, depend upon formation of new blood vessels. Our research seeks to identify novel factors regulating blood vessel growth. In this context we have examined the role of proteins that mediate communication between cells, called connexins. By increasing our understanding of the factors affecting blood vessel growth we learn how to create novel therapies to enhance the treatment of ischemic disease and cancer.
Role Of Microparticles In Cardiac Ischemia Reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$55,575.00
Summary
Interventional cardiology has reduced the mortality rate associated with heart attack, unfortunately the prevalence of heart failure has subsequently increased, caused in part by reperfusion injury of previously occluded vessels. We aim to identify novel insights into the pathogenesis of IR injury in the heart, as well as the development of new approaches to prevent cardiac damage during cardiac surgery, transplantation, post-angioplasty and coronary artery stenting.
Relationship Between Cell-cell Interactions And Disease Severity In Patients With Cerebral Malaria
Funder
National Health and Medical Research Council
Funding Amount
$545,183.00
Summary
Severe malaria is a collection of disease complications that leads to about 2 million deaths each year worldwide. Young children in Africa and young adults in several parts of South-East Asia are particularly affected. Travellers to these regions are also at considerable risk. One of the most dangerous complications of malaria is when the brain becomes affected, which is called cerebral malaria. We still do not understand enough about the changes that link the parasite circulating in the blood w ....Severe malaria is a collection of disease complications that leads to about 2 million deaths each year worldwide. Young children in Africa and young adults in several parts of South-East Asia are particularly affected. Travellers to these regions are also at considerable risk. One of the most dangerous complications of malaria is when the brain becomes affected, which is called cerebral malaria. We still do not understand enough about the changes that link the parasite circulating in the blood with the devastating disturbance of brain function that causes death in some people who develop cerebral malaria. In this project we will investigate some new ideas about how cerebral malaria develops. We will perform a detailed study of brain tissue taken from victims of cerebral malaria and compare the observations with similar ones in children who died of other causes. Then we will work with an experimental model we have developed, in which we put together in culture flasks the various types of cell that are found in the brain lesions in people who die from cerebral malaria. Our aim is to identify some new therapeutic targets for later use in treatment of cerebral malaria patients.Read moreRead less
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.
Bench To Beside Translational Studies To Develop Treatments For Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$265,138.00
Summary
Preeclampsia is a common, devastating complication of pregnancy responsible for the loss of countless mothers and babies. There is no medical treatment. Excitingly we have identified 2 medications, safe in pregnancy: metformin and sulfasalazine that may treat this disease. We plan to introduce these medications into the clinic to see whether they may be an effective treatment for preeclampsia. If successful, these medications have the potential to improve the lives of women and babies globally.