Formation, Structure And Metabolism Of High Density Lipoproteins Containing Both ApoAI And ApoAII On The Same Particle
Funder
National Health and Medical Research Council
Funding Amount
$296,884.00
Summary
It is well known that high levels of cholesterol in blood cause coronary heart disease. It is also known that not all of the cholesterol in blood is bad. Whereas the cholesterol carried in particles called low density lipoproteins (LDLs) causes heart disease, other cholesterol carriers in blood known as high density lipoproteins (HDLs) actually protect against the development of heart disease. However, HDLs include several different populations of particles, only some of which are protective. On ....It is well known that high levels of cholesterol in blood cause coronary heart disease. It is also known that not all of the cholesterol in blood is bad. Whereas the cholesterol carried in particles called low density lipoproteins (LDLs) causes heart disease, other cholesterol carriers in blood known as high density lipoproteins (HDLs) actually protect against the development of heart disease. However, HDLs include several different populations of particles, only some of which are protective. One determinant of the ability of HDLs to protect against coronary heart disease is their protein composition. This project investigates how the protein composition of HDL populations influences their structure, function and metabolism. It is also concerned with understanding what regulates the relative concentrations of the different HDL populations. The studies of HDL structure, function and metabolism will allow us to understand why the different HDL populations differ in their abilities to protect against heart disease. The regulation studies will tell us how to go about designing therapies to increase the levels of those HDL populations that do protect.Read moreRead less
I am a lipid biochemist-cell biologist determining the molecular mechanisms of disorders of lipid metabolism and developing treatments for such disorders. The diseases where lipid metabolism plays a key role include cardiovascular diseases (such as coronary artery disease), metabolic disorders (such as diabetes), some infectious diseases (such as HIV) and neurological disorders (such as Alzheimer disease).
Multifunctional Regualtion Of Angiogenesis By High Density Lipoproteins
Funder
National Health and Medical Research Council
Funding Amount
$480,653.00
Summary
For many sufferers of heart disease and cancer, current treatments do not relieve the debilitating symptoms. The growth of new blood vessels can alleviate the effects of a restricted blood supply, caused by blocked arteries. Conversely, new vessel growth accelerates some diseases such as cancer. HDL is one of the main forms of cholesterol in the blood. Recently we identified a beneficial bifunctional role for HDL in vessel growth. This project will investigate the mechanisms for these effects.
HDL Elevation And Glucose Metabolism: A Mechanistic Proof-of-Concept Intervention Trial In Pre-Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$507,974.00
Summary
This clinical trial will investigate a new treatment strategy for type 2 diabetes. Building on our novel discovery that HDL (good cholesterol) lowers blood glucose, we will test whether HDL elevation over a month with a new drug (RVX-208) can improve glucose control in patients with pre-diabetes. If positive, these studies will support new therapeutic approaches to raise levels of circulating HDL for indications beyond vascular disease to manage type 2 diabetes.
Clinical Innovation Through Multidisciplinary Metabolic And Vascular Physiology: Impact Across The Obesity, Diabetes And Cardiovascular Disease Continuum
Funder
National Health and Medical Research Council
Funding Amount
$863,413.00
Summary
This innovative research program will address important clinical questions across the obesity, diabetes & cardiovascular disease continuum. Outcomes are directed to novel preventive, diagnostic & therapeutic strategies using a multidisciplinary approach. Potential major outcomes: 1. Novel therapies for diabetes by elevating good cholesterol 2. New anti-obesity strategies by stimulating brown fat 3. Drugs to manage peripheral artery diseases 4. A diagnostic test for sudden heart attacks
Obesity And Protective Properties Of High-Density Lipoproteins
Funder
National Health and Medical Research Council
Funding Amount
$391,265.00
Summary
High-density lipoproteins (HDL) are the good form of cholesterol and protect against heart disease. Obesity is associated with a high risk of heart disease and low HDL levels. The effects of obesity on the ability of HDL to prevent plaque build up in the artery wall has not been studied. This project will study how obesity affects the ability of HDL to stop plaque formation. This will provide important information linking two major health problems in Australia, obesity and heart disease.
Suppression Of NADPH Oxidase-derived Oxidative Stress By Anti-sense Probes And HDL In Human Vascular Endothelium
Funder
National Health and Medical Research Council
Funding Amount
$455,250.00
Summary
In Australia, coronary heart disease (CHD) causing heart attacks remains the largest cause of death, claiming a staggering 28,000 lives a year. Oxidative stress, resulting from increased production of oxygen free radicals in arteries, is an important cause of CHD, heart attacks and strokes. We seek to understand how such oxyradicals are produced in the key cells that form the lining of all arteries, known as the vascular endothelium. By using novel DNA-type molecules (known as anti-sense) develo ....In Australia, coronary heart disease (CHD) causing heart attacks remains the largest cause of death, claiming a staggering 28,000 lives a year. Oxidative stress, resulting from increased production of oxygen free radicals in arteries, is an important cause of CHD, heart attacks and strokes. We seek to understand how such oxyradicals are produced in the key cells that form the lining of all arteries, known as the vascular endothelium. By using novel DNA-type molecules (known as anti-sense) developed in our laboratory, which block a particular gene causing oxidative stress, we will determine whether this gene is responsible for the formation of oxyradicals in human and mouse cells grown in culture. In addition, we will explore whether this gene is turned on by factors known to be involved in CHD. Finally, we will also investigate whether the good cholesterol known as HDL can act to prevent oxidative stress in human cells, as we discovered it appears to do in living arteries in vivo. If we find it has the same protective effect in endothelium, we will determine how it does this, and which component proteins of the HDL particle are important. This might suggest new treatments to prevent acute events leading to heart attack and stroke, and possibly new applications where damage appears to result from acute oxidative stress, such as in the brain soon after a stroke has occurred. We also have a plan to develop antisense drugs that will target the important gene specifically in the affected endothelium. In addition, we have other specific new drugs that will block this system in arteries. Simultaneously we will be testing the role of this gene in mouse and rabbit models of artery disease, for both our types of drugs might provide valuable new therapeutic agents to target the underlying cause of CHD and not just its symptoms as current drugs do.Read moreRead less
Novel Strategies In Cancer Cell Invasion In High-density 3D Matrix
Funder
National Health and Medical Research Council
Funding Amount
$60,768.00
Summary
The use of high-density (HD) matrix to study cell invasion sets precedence in mimicking the HD breast tissue condition that pose a real cancer risk. Cell invasion promotes the spread of cancer causing organ failures and death. The aims of this project are to determine the molecular mechanisms and to isolate new regulatory markers of cell invasion into HD matrix. Putative markers will be confirmed by investigating their expression levels in tissue arrays of 195 breast cancer samples.