Novel Apolipoprotein A-I Mimetic Peptides: A Research Tool And A Therapeutic Agent To Study And Treat Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$266,387.00
Summary
Drugs affecting lipid metabolism have revolutionized the treatment of heart diseases. There is, however, an urgent need for further reduction of high remaining risk. A most promising direction is increasing levels of _good cholesterol�. A new type of such therapy are simple compounds mimicking structure of good cholesterol. We have synthesized new such compounds that are even more active than good cholesterol. Now we will test these compounds in animals and in clinical trial.
Depression And Risk Of Coronary Heart Disease: A Prospective Study Of Mediating Haemostatic Risk Factors
Funder
National Health and Medical Research Council
Funding Amount
$327,625.00
Summary
Growing evidence suggests that depression, anger and anxiety play a role in causing coronary heart disease (CHD) and complicating the outcome in existing CHD. This may occur by effects of these emotions on promoting blood clotting and the stickiness of platelets - the blood cells responsible for blood clotting. This pilot study will follow a group of people with depression but without CHD and a control group over 8 months to compare how the blood clotting profile changes as depression resolves. ....Growing evidence suggests that depression, anger and anxiety play a role in causing coronary heart disease (CHD) and complicating the outcome in existing CHD. This may occur by effects of these emotions on promoting blood clotting and the stickiness of platelets - the blood cells responsible for blood clotting. This pilot study will follow a group of people with depression but without CHD and a control group over 8 months to compare how the blood clotting profile changes as depression resolves. The potential benefits of this research are a better understanding of the links between the common illnesses of depression and CHD that might improve the prevention and treatment of heart disease.Read moreRead less
This project studies the mechanisms involved in rejection of skin and heart grafts using a novel model to track the behaviour of individual graft-reactive white blood cells. We will test two promising new techniques to limit graft rejection: using drugs to inhibit the entry of graft-reactive cells into the graft, and administering cells with the ability to suppress the function of graft-reactive cells. This work will help us to design new therapies to prevent heart graft rejection.
Intracellular Cholesteryl Ester Hydroperoxides And Hydroxides- Their Metabolism And Their Modulation Of Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$182,029.00
Summary
Atherosclerosis is the disease which causes narrowings in arteries underlying such serious medical conditions as heart attack and stroke. A key component in the formation of atherosclerotic narrowings is the accumulation of fat-filled cells called foam cell macrophages in artery walls. Our study investigates the nature of the fats that macrophages accumulate, and how mild modification of these fats changes the metabolism of the macrophage. Cholesterol circulates in the blood stream as specialise ....Atherosclerosis is the disease which causes narrowings in arteries underlying such serious medical conditions as heart attack and stroke. A key component in the formation of atherosclerotic narrowings is the accumulation of fat-filled cells called foam cell macrophages in artery walls. Our study investigates the nature of the fats that macrophages accumulate, and how mild modification of these fats changes the metabolism of the macrophage. Cholesterol circulates in the blood stream as specialised particles called lipoproteins. The lipoprotein containing most of the cholesterol is low density lipoprotein (LDL), so-called bad cholesterol. LDL is the main source of fat that accumulates in the artery wall in atherosclerosis. When in the artery wall, it is taken up by macrophages which develop a foamy appearance. The accumulation of LDL fats within macrophages is greatly enhanced by the prior modification of LDL. The most well known of these modifications is oxidation- a chemical process of fat spoilage as occurs with rancid butter. Mild oxidation of LDL is well known to occur in human atherosclerosis. However, the ability of macrophages to accumulate the products of mild oxidation has never been established. We have recently discovered that the lipid products of mild oxidation of LDL can build up in macrophages. We achieved this by developing a new system of feeding oxidised LDL to macrophages. Surprisingly, not only could these lipid oxidation products be internalised by the cells, but they progressively accumulated over time, and caused major disturbances in the ability of macrophages to clear ordinary fats inside the cell. This means that mild oxidation of LDL can cause secondary damage inside the macrophage, which is far greater than had previously been realised. This project investigates precisely how the oxidised LDL is metabolised by macrophages and how it disturbs other cell functions.Read moreRead less
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
Physiology Of A Mutant Angiotensin Receptor Associated With Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$293,699.00
Summary
As many as one in ten healthy individuals have hearts that are bigger than normal. Careful scientific investigation has revealed that the bigger one's heart, the greater the risk of dying from cardiovascular disease. This is true even in the absence of known causes of heart disease. Unlike high blood pressure or cholesterol, the size of the heart is not easily measured and enlargement often goes undetected. We were among the first internationally to discover genetic clues to enlarged hearts. We ....As many as one in ten healthy individuals have hearts that are bigger than normal. Careful scientific investigation has revealed that the bigger one's heart, the greater the risk of dying from cardiovascular disease. This is true even in the absence of known causes of heart disease. Unlike high blood pressure or cholesterol, the size of the heart is not easily measured and enlargement often goes undetected. We were among the first internationally to discover genetic clues to enlarged hearts. We identified a region on a rat chromosome that influences heart size and we have now discovered abnormalities in a key gene in this region. These changes alter the function of a cellular protein that mediates hormonal effects on heart cell size. Our team of experts will employ the most modern technologies to understand exactly how this altered protein affects heart cell function and growth. We have a unique opportunity to exploit this experiment of nature to help us devise new means of preventing big hearts and their fatal complications in humans.Read moreRead less
Statistical Methods For The Analysis Of Trends In Coronary Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$112,747.00
Summary
Coronary heart disease is a leading cause of mortality, morbidity and medical costs in Australia. During the 1950's and 1960's, rates of coronary disease increased rapidly, then in the late 1960's they started to decline. This decrease has continued steadily for 30 years. While some other westernised countries have had this same experience, in Eastern Europe and in many developing countries coronary disease is increasing. There is a huge amount of evidence from experimental studies in animal and ....Coronary heart disease is a leading cause of mortality, morbidity and medical costs in Australia. During the 1950's and 1960's, rates of coronary disease increased rapidly, then in the late 1960's they started to decline. This decrease has continued steadily for 30 years. While some other westernised countries have had this same experience, in Eastern Europe and in many developing countries coronary disease is increasing. There is a huge amount of evidence from experimental studies in animal and human subjects and population studies in many countries that the major determinants of coronary disease are high blood pressure, cigarette smoking and high cholesterol (and other lipids) as well as dietary factors, obesity and physical inactivity. Recently several large multicentre studies have found unexpectedly weaker associations between heart risk factors and disease rates. It is hypothesised that this is due to inappropriate analyses in which data from populations at different stages of the coronary epidemic have been combined. The aim of this study is to develop improved statistical methodology to help understand recent findings from large scale studies, such as the World Health Organization's MONICA Project, the US ARIC study and the Seven Countries study. It will provide new theoretical results and statistical software for their implementation. From a public health perspective the most important outcome will be clarification of recent apparently anomalous findings about the importance of established risk factors and effective treatments in reducing coronary disease at the population level.Read moreRead less
Increasing Cardiovascular Risk Assessment In First Degree Relatives Of Patients With Premature Heart Disease: An RCT
Funder
National Health and Medical Research Council
Funding Amount
$113,972.00
Summary
Family history is a risk factor for ischaemic heart disease (IHD), especially if the history includes early onset disease. Families share both genetic and environmental risk factors, many of which can be modified to reduce the risk of heart disease. The aim of this project is to trial an intervention to promote heart disese risk assessment among the relatives of patients with premature heart disease. This is a first step toward prevention of heart disease in these families.
Towards A New Normokalemic Arrest Paradigm For Orthotopic Heart Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$489,634.00
Summary
Innovations from Nature to Heart Transplantation:a Real Heart Stopper Heart preservation is limited to 4-6 hours of cold-ischaemic storage (0 to 4 C). The risk of post-transplant death doubles if the donor heart is stored from 1 to 5 hours, and triples with 7 hrs storage times. We have developed a new preservation solution borrowing from natural hibernators that will permit organs to be safely stored for up to 15 hours, and offering new opportunities to organ donors and recipients worldwide.
Does Oxidation Of Lipoproteins By Thiocyanate-derived Oxidants Produced By Myeloperoxidase Contribute To Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$357,930.00
Summary
Considerable evidence links the heme enzyme myeloperoxidase with atherosclerosis (hardening of the arteries), a disease that kills approximately 40% of Australians, and particularly people who smoke. The reasons for the elevated risk in smokers is not fully understood, though it is known that they have elevated thiocyanate levels - a major substrate for myeloperoxidase. The role of myeloperoxidase and thiocyanate in lipoprotein damage in atherosclerosis will be addressed in this project.