The Effect Of Stress/strain And Fatigue Fracture Sites On Durability Of Modular Aortic Endografts And Arterial Walls
Funder
National Health and Medical Research Council
Funding Amount
$300,919.00
Summary
Aneurysmal disease is an age related phenomenon. The mean life expectancy of western populations has doubled in 100 years because of the reduction in deaths from preventable and treatable diseases, and prolongation of life with chronic and incurable diseases. The older community (>65 years) continues to be active and productive contrary to prior predictions. Aneurysmal disease has emerged as a result of the changing pattern of diseases in the community. As with many other diseases, prophylaxi ....Aneurysmal disease is an age related phenomenon. The mean life expectancy of western populations has doubled in 100 years because of the reduction in deaths from preventable and treatable diseases, and prolongation of life with chronic and incurable diseases. The older community (>65 years) continues to be active and productive contrary to prior predictions. Aneurysmal disease has emerged as a result of the changing pattern of diseases in the community. As with many other diseases, prophylaxis against aneurysmal disease is the most effective approach since 80% of those that rupture will result in death. Endoluminal grafting provides a much less invasive procedure and provides an attractive and elegant alternative to open surgery. The danger is that structural strengths will be compromised with failures due to lack of strength and inadequate device durability. The most practical endografts are those that are built up from modules but vulnerable sites affected by fatiguing and disruptive forces are being identified, in particular where a tube divides into two outflow channels – the bifurcation - and joins. To improve and protect the current device, and enable sound engineering for future devices, we need to know the nature, magnitude and location of these forces. The existing collaboration with medical specialist, Cook Aust., the Advanced Fluid Dynamics Laboratory (CSIRO, Melb.) and University of WA combines a multidisciplinary team working towards the design and durability of the next generation of endoluminal devices and percutaneous insertions. While Australia is at the forefront of development, its current place in the market can only be maintained by further product development. Optimising and improving endoluminal grafts will reduce the suffering of major surgery while prolonging a higher quality of life with a much less invasive procedure whose long-term effectiveness, and thereby acceptance is dependent upon reliable durability.Read moreRead less
Antioxidant Glutathione Peroxidase (GPx) Mimetics And Atherosclerosis: A Role For Targeted Antioxidant Therapy.
Funder
National Health and Medical Research Council
Funding Amount
$358,319.00
Summary
This proposal investigates the use of antioxidant therapy, targeted at increasing the function of the body's important antioxidant enzyme GPx1, to reduce atherosclerosis both in a non-diabetic and diabetic setting. Strong clinical evidence and our recently published data support an important role for GPx1 in limiting atherosclerosis. We will now investigate the molecular mechanisms involved in mediating these effects and whether compounds that mimic GPx1 function reduce atherosclerosis.
Atherosclerosis (hardening of the arteries) is the principal cause of heart attack, stroke and blockage of blood flow to the lower limbs. However, to date none of the biological or synthetic grafts used to bypass the narrowed regions of arteries is ideal. We have shown that lengths of silicone tubing placed into the peritoneal cavity of rats or rabbits becomes covered within 2 weeks by a capsule of granulation tissue (smooth-muscle-like cells and collagen) and mesothelial (endothelial-like) cell ....Atherosclerosis (hardening of the arteries) is the principal cause of heart attack, stroke and blockage of blood flow to the lower limbs. However, to date none of the biological or synthetic grafts used to bypass the narrowed regions of arteries is ideal. We have shown that lengths of silicone tubing placed into the peritoneal cavity of rats or rabbits becomes covered within 2 weeks by a capsule of granulation tissue (smooth-muscle-like cells and collagen) and mesothelial (endothelial-like) cells. The silicone tubing can be removed and the tissue turned inside out such that the endothelial-like cells now line the inside of the tube of living tissue, which resembles a blood vessel. These artificial blood vessels will be grown in the peritoneal cavity of rabbits, then grafted into the right carotid artery to replace a length of removed vessel. Their long-term (3,6,9 and 12 months) patency, reactivity, tensile strength and resistance to clot development will be assessed. Their susceptibility to atherosclerotic plaque development and blockage (as compared with natural carotid artery) will be examined in rabbits fed a cholesterol-enriched diet. Changes in gene expression as the artificial artery progressively develops will be examined, as will the potential to genetically manipulate the artificial artery to improve its functioning. Finally, attempts will be made to grow the vessels entirely in vitro. This novel vascular graft may open new options in the field of arterial reconstructive surgery for replacing or bypassing diseased vessels or as an access vessel for haemodialysis patients with end stage renal failure. This study will also provide new information on the biology of cells found in the peritoneal cavity and their alternative pathways for differentiation.Read moreRead less
Oxidative Stress, Heparan Sulfates And Endothelial Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$450,390.00
Summary
During vascular disease endothelial cells that line the blood lumen are dysfunctional. Growing evidence indicates a role for a protein that the immune system normally uses to destroy infectious agents. This protein accumulates in diseased blood vessels next to endothelial cells. This project will study how this protein causes endothelial dysfunction and test the ability of novel agents to remove this protein from diseased blood vessels to improve endothelial function.
Atherosclerosis: Molecular Mechanisms Of Suppression By CD4+CD25+ Regulatory T-cells
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
Atherosclerosis, or hardening of large arteries is the underlying cause of up to 50% of deaths in Western communities, primarily from heart attacks and strokes. Today it is considered a chronic inflammatory disease arising from the accumulation of fats such as cholesterol into the inner lining of blood vessels including those supply vital organs such as the heart and brain. This study focuses on understanding how to use the body's own anti-inflammatory cells suppress inflammation.
The Role Of Dysregulated VEGFs In Lymphatic And Non-lymphatic Vascular Malformations
Funder
National Health and Medical Research Council
Funding Amount
$389,486.00
Summary
Vascular malformations are abnormal growths of blood vessels that affect hundreds of children born in Australia every year. They range from small birthmarks to large destructive growths that cause chronic pain, bleeding and major deformity. This is the largest ever study to systematically look for the biological drivers that cause these growths so that drug treatments will ultimately be able to replace surgery as the first line treatment.
Minimal Structural Strength Required In Endoluminal Devices For Aortic Aneurysms: Mechanisms Of Rupture When They Fail.
Funder
National Health and Medical Research Council
Funding Amount
$102,794.00
Summary
Aneurysmal disease is an age related phenomenon. The mean life expectancy of western populations has doubled in the last 100 years mainly because of the reduction in deaths from occlusive cardiovascular disease. Aneurysmal disease has emerged as a result of the changing pattern of diseases in the community. The impact of this work would be to improve minimally invasive, effective prophylaxis against aneurysm of the abdominal aorta since 80% of those that rupture will result in death. Endoluminal ....Aneurysmal disease is an age related phenomenon. The mean life expectancy of western populations has doubled in the last 100 years mainly because of the reduction in deaths from occlusive cardiovascular disease. Aneurysmal disease has emerged as a result of the changing pattern of diseases in the community. The impact of this work would be to improve minimally invasive, effective prophylaxis against aneurysm of the abdominal aorta since 80% of those that rupture will result in death. Endoluminal grafting provides a much less invasive procedure and provides an attractive and elegant alternative to open surgery. The general drive in this field is towards miniaturisation. The danger is that structural strengths will be compromised with early failures due to lack of strength; and late failures due to inadequate device durability. This application proposes the development of a collaborative venture with the Department of Vascular Surgery, Royal Perth Hospital, Cook R and D (WA), the Advanced Fluid Dynamics Laboratory (CSIRO, Melbourne) and Centre for Health Services Research (University of WA) to investigate the dynamic flow forces involved in aneurysms of the abdominal aorta. It combines together expertise and facilities to examine the forces acting upon endoluminal stent grafts in pulsatile high pressure environments, the impact on the design, patency, effectiveness and longer-term outcomes. The multidisciplinary team provides a comprehensive approach for this developing area of high technology surgery throughout Australia and internationally. The benefits of this study will directly influence the design and durability of the next generation of endoluminal devices and percutaneous insertions. While Australia is at the forefront of development, its current place in the market can only be maintained by further product development.Read moreRead less
Monomeric C-reactive Protein As Pathogenic Factor And Therapeutic Target In Athero-thrombotic Disease.
Funder
National Health and Medical Research Council
Funding Amount
$86,570.00
Summary
Vascular disease of the heart, brain and limbs affects many people in Australia and throughout the world. Current treatments assist in slowing the development and progression of established disease, but new developments are required. This project will investigate the role of C-reactive protein in vascular disease and evaluate its potential as a new therapeutic target in the future.
Atherosclerosis:Lipoproteins, Cell Biology And Vascular Physiology
Funder
National Health and Medical Research Council
Funding Amount
$7,274,391.00
Summary
The team comprises internationally recognised experts in basic, clinical and public health applied research in cardiovascular disease, particularly atherosclerosis that is the commonest cause of death in Australia and other developed countries. Over the last decade, improvement in cardiovascular health has been primarily the result of a better understanding on how to control 'bad' (or LDL) cholesterol. The significance of the proposed studies is that, on the one hand, they will provide new infor ....The team comprises internationally recognised experts in basic, clinical and public health applied research in cardiovascular disease, particularly atherosclerosis that is the commonest cause of death in Australia and other developed countries. Over the last decade, improvement in cardiovascular health has been primarily the result of a better understanding on how to control 'bad' (or LDL) cholesterol. The significance of the proposed studies is that, on the one hand, they will provide new information on how 'good' lipoproteins protect us from atherosclerosis. This information can then be used to regulate 'good' cholesterol in a meaningful manner. On the other hand, the proposed studies will provide fundamental insights into how a range of lifestyle factors, physiological processes and pathological conditions relate to both the function of blood vessel-lining cells and susceptibility of individuals to atherosclerosis.Read moreRead less