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.
Identification Of Heterogeneity In Vasodilator Function In Human And Rat Resistance Vessels: Potential Drug Targets?
Funder
National Health and Medical Research Council
Funding Amount
$595,330.00
Summary
The balance between the ways that blood vessels decrease in size (constrict) and increase in size (dilate) determine how blood vessels normally function. There are many differences in the ways that blood vessels control this balance in different parts of the body. Such differences are altered in vascular diseases, such as hypertension and diabetes, which are prevalent in obesity, such that constriction generally outweighs dilation. However, what these differences are and how they occur are not w ....The balance between the ways that blood vessels decrease in size (constrict) and increase in size (dilate) determine how blood vessels normally function. There are many differences in the ways that blood vessels control this balance in different parts of the body. Such differences are altered in vascular diseases, such as hypertension and diabetes, which are prevalent in obesity, such that constriction generally outweighs dilation. However, what these differences are and how they occur are not well understood. While current drugs for treating vascular disease either reduce vessel constriction or increase dilation, they are not specific for individual arteries; a situation that would allow us to control vascular diseases in a very specific manner. Recently, we have described differences between the ways that individual vessels are controlled. These changes relate to differences in the way that different vessels dilate. AIMS - To further understand normal blood vessel function and the changes that occur in blood vessels in cardiovascular disease, with a focus on the ways that blood vessels dilate in normal states and in obesity-related diseases, such as in hypertension and diabetes. - The eventual aim is to identify the specific ways that arteries function, so that artery-specific drug targets can be identified to treat disease-related changes in cardiovascular disease in a very specific manner. EXPECTED OUTCOMES This project will contribute to understanding blood vessel function in health and disease. The expected eventual outcome is the identification of the mechanisms that underlie the function of different arteries in different parts of the body, so that specific individual vessel function can be targeted to treat vascular disease. Additionally, this work will also verify the relevance of the diet-induced obesity animal model, in terms of the characteristics and causes of human obesity and related cardiovascular disease.Read moreRead less
Development Of Recombinant RsolCD39-PSGL As A Novel Therapeutic With Anti-thrombotic And Anti-inflammatory Effects
Funder
National Health and Medical Research Council
Funding Amount
$186,367.00
Summary
Heart disease and stroke are due to a narrowing of arteries followed by occlusion, due a combination of clot formation initiated by platelet clumping, and inflammation surrounding the vessel wall. The currently available drugs are often limited by the adverse reaction of bleeding. We will investigate the efficiency of a new drug to prevent clot formation and inflammation.
Development Of An Antibody-targeted Drug/miRNA/peptide Delivery System For Effective Prevention Of Restenosis
Funder
National Health and Medical Research Council
Funding Amount
$319,064.00
Summary
The re-blocking of vessels after surgery occurs up to 50% of patients, and none of the preventive approaches are cost-effective and safe enough. This project aims to develop a nano-scaled therapeutics delivering combination therapies to effectively prevent the re-blockage after surgery. If successful, this research will present a whole new range of therapeutic agent that prevents the patient from developing clots after surgery, improving the productivity and health of patients with reduced cost.
The prevalence of heart disease and stroke is increasing in the affluent world. These disorders are due to a narrowing of arteries due to clot formation, thereby reducing available blood supply to the heart and brain. Blood vessel occlusion is due a combination of clot formation initiated by platelet clumping, and inflammation surrounding the vessel wall. Drugs that prevent the clumping of platelets on the inner lining of the blood vessels play an important role in the prevention and treatment o ....The prevalence of heart disease and stroke is increasing in the affluent world. These disorders are due to a narrowing of arteries due to clot formation, thereby reducing available blood supply to the heart and brain. Blood vessel occlusion is due a combination of clot formation initiated by platelet clumping, and inflammation surrounding the vessel wall. Drugs that prevent the clumping of platelets on the inner lining of the blood vessels play an important role in the prevention and treatment of heart attack and stroke. The currently available drugs are not universally effective and their use is often limited by adverse reactions. In this submission, we propose to investigate the efficiency of a new drug that will prevent clot formation and will also tackle inflammation. This drug is a derivative of an enzyme that is already present on platelets and cells that line blood vessels. We have modified this enzyme in a manner that will increase the enzyme activity on the surface of platelets and on the cells that line the blood vessel wall. We will thoroughly study this new drug by performing experiments in the laboratory as well as by studying its effect in mice.Read moreRead less
Myoendothelial Gap Junctions: Their Composition And Role In Vasodilator Responses Attributed To EDHF
Funder
National Health and Medical Research Council
Funding Amount
$282,750.00
Summary
Cardiovascular disease, including coronary heart disease and stroke, continues to be the major cause of death in Australia and hypertension is a significant risk factor. The endothelium, which lines blood vessels of all sizes, is critical to the control of blood flow to the organs of the body. Endothelial cells release factors which can cause blood vessels to constrict or to relax, thus decreasing or increasing blood flow, respectively. Under normal conditions, the endothelium is more important ....Cardiovascular disease, including coronary heart disease and stroke, continues to be the major cause of death in Australia and hypertension is a significant risk factor. The endothelium, which lines blood vessels of all sizes, is critical to the control of blood flow to the organs of the body. Endothelial cells release factors which can cause blood vessels to constrict or to relax, thus decreasing or increasing blood flow, respectively. Under normal conditions, the endothelium is more important as a source of relaxing factors, while under hypertensive conditions, the balance is shifted in favour of the release of constricting factors. Thus, restoration of the vasodilatory function of the endothelium is seen as an important new therapeutic target in the treatment of vascular disorders. Present data suggests that the action of one of the major endothelial derived vasodilatory factors, the so-called endothelium-derived hyperpolarizing factor, EDHF, requires the presence of particular structures within the vascular wall, but little is known about the molecules of which they are comprised. We have identified two unique situations, during development and during hypertension, when these structures are present in vessels in which they are absent in normal adults. We will use gene microarrays to identify the specific molecules involved in these structures and use physiological studies to test the role of these proteins and structures in vasodilatory responses. The results of these studies may identify new targets for therapeutic intervention to restore the action of EDHF in hypertension.Read moreRead less
Microvascular Function And Outcome In Patients With Acute Coronary Syndromes
Funder
National Health and Medical Research Council
Funding Amount
$79,514.00
Summary
Damage to the small vessels of the heart is a hallmark of heart attacks. Furthermore, small vessel dysfunction (MVD) is associated with a worse prognosis even in the presence of an unblocked major coronary artery following a heart attack. Using novel invasive assessments, we aim to analyse the prevalence and clinical predictors of MVD, assess the impact of MVD on short and long-term outcome after heart attack and address the impact of new treatments on MVD and heart muscle recovery.
This study is testing two drugs in people having heart surgery, to see whether either can reduce serious complications such as heart attack, stroke or death. Aspirin thins the blood and can reduce these risks but it increases bleeding during surgery. Another drug can reduce bleeding, but it may counteract the benefits of aspirin. The study is being done at more than 20 hospitals in Australia and around the world.
Studying Coronary Physiology Within Human Coronary Arteries Using Computational Fluid Dynamics
Funder
National Health and Medical Research Council
Funding Amount
$383,834.00
Summary
The aim of this project is to combine the recent technological advances within the individual fields of coronary physiology, three-dimensional coronary angiography, and computational fluid dynamics to develop a novel method to calculate realistic coronary blood flow. This technique will provide a simple and clinically applicable method to measure physiological parameters such as microcirculatory resistance and shear stress within _live� human coronary arteries.