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
Microvascular And Macrovascular Disease In Snoring And Obstructive Sleep Apnoea: A Mechanism For Increased Stroke Risk.
Funder
National Health and Medical Research Council
Funding Amount
$679,744.00
Summary
This project will address the important question of the vascular risk of stroke associated with snoring and obstructive sleep apnoea, by using retinal photography of the eye to directly visualise the vascular changes in the cerebral circulation. Retinal photography may provide a useful clinical tool to help reduce the risk of stroke in patients with snoring and sleep apnoea.
STudy Of Risk Assessment To Reduce Complications In Patients Following Noncardiac SurgerY (STRATIFY)
Funder
National Health and Medical Research Council
Funding Amount
$436,000.00
Summary
Cardiac problems account for many complications in patients undergoing major non-cardiac surgery, and even apparently minor cardiac damage is a marker of high risk for subsequent adverse events. Unfortunately, while money and effort is expended on identifying patients at risk, the appropriate response to this risk is quite unclear. The performance of bypass surgery or balloon angioplasty in order to treat the underlying coronary disease of at-risk patients is used in other situations, and reduce ....Cardiac problems account for many complications in patients undergoing major non-cardiac surgery, and even apparently minor cardiac damage is a marker of high risk for subsequent adverse events. Unfortunately, while money and effort is expended on identifying patients at risk, the appropriate response to this risk is quite unclear. The performance of bypass surgery or balloon angioplasty in order to treat the underlying coronary disease of at-risk patients is used in other situations, and reduces longterm risk. However, in many patients undergoing major noncardiac surgery, this approach may be inappropriately aggressive, as these patients are often elderly, have other diseases that make heart operations more difficult and risky than usual, and in any case may have a reduced life expectancy from the disease necessitating the operation. As the most critical issue is to ensure that patients undergo their surgery uneventfully, an alternative is the use of intensive medical therapy to protect the heart. This multicentre study, based at Brisbane hospitals that perform large numbers of major operations, will follow up patients for complications, and outcome (including quality of life) will be assessed six months after the operation. We will address two important questions about the efficacy and cost of risk reduction strategies. First, in patients at higher levels of risk and with a positive stress test, could a combination of medical therapy designed to protect the heart be as effective as current approaches, which include the performance of bypass surgery or coronary balloon angioplasty? Second, in patients identified as being at some risk - but low risk - are drugs sufficiently effective to avoid the need for further testing to quantify risk? As the population continues to age, the numbers of at risk patients undergoing major surgery will increase, and answers to these questions will provide important information to guide their management.Read moreRead less
A-Prof Wheatley is a respiratory and sleep disorders physician investigating the pathogenesis, health consequences and management of sleep breathing disorders, including sleep apnoea and snoring.
Understanding glycopolymer interactions with the extracellular matrix. This project aims to advance knowledge of the biochemical and biophysical structure of the endothelial glycocalyx, a dynamic cell surface extracellular matrix rich in proteoglycans and glycosaminoglycans. It will be the first to explore how charged glycopolymers interact with this dynamic interface with the goal to develop a model of the glycocalyx lifecycle. This project is expected to enable the transfer of skills, knowledg ....Understanding glycopolymer interactions with the extracellular matrix. This project aims to advance knowledge of the biochemical and biophysical structure of the endothelial glycocalyx, a dynamic cell surface extracellular matrix rich in proteoglycans and glycosaminoglycans. It will be the first to explore how charged glycopolymers interact with this dynamic interface with the goal to develop a model of the glycocalyx lifecycle. This project is expected to enable the transfer of skills, knowledge and ideas as well as advanced research and industrial training for young scientists. Knowledge derived from this project is expected to enable future innovation in molecules with tailored interactions with the glycocalyx with significant benefits for researchers, manufacturers and end users. Read moreRead less
Engineering nanomaterial interactions with the cell surface. This Fellowship aims to advance understanding of the endothelial cell surface, a key tissue barrier, and its interactions with nanomaterials. Enabled by cross-disciplinary collaboration, it expects to develop knowledge in matrix biology of the cell surface and materials as well as new methods to analyse their interactions. This is expected to unravel causal relationships between nanomaterial features and interactions at the cell surfac ....Engineering nanomaterial interactions with the cell surface. This Fellowship aims to advance understanding of the endothelial cell surface, a key tissue barrier, and its interactions with nanomaterials. Enabled by cross-disciplinary collaboration, it expects to develop knowledge in matrix biology of the cell surface and materials as well as new methods to analyse their interactions. This is expected to unravel causal relationships between nanomaterial features and interactions at the cell surface which will be integrated to engineer optimised materials. This will address the current and critical challenges of nanomaterial technologies in the efficient and targeted interactions with cells with long-term benefits for the consumer, biotechnology and healthcare sectors.Read moreRead less
The Impact Of CPAP Treatment On Carotid Artery Atherosclerosis In Heavy Snoring And Mild Sleep Disordered Breathing
Funder
National Health and Medical Research Council
Funding Amount
$697,512.00
Summary
Mild sleep disordered breathing, including habitual snoring, is a very common problem in the adult population, with a prevalence of between 20-40%. Increasingly it is now recognised that habitual snoring may be an independent risk factor for the development of stroke. In this proposal we will explore the hypothesis that treatment for snoring will slow or stop the development of carotid artery atherosclerosis.