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Targetting The NADPHoxidase Source Of Reactive Oxygen Species In Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$552,250.00
Summary
In Australia, coronary heart disease (CHD) leading to heart attacks or strokes is 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, appears to be an important cause of CHD, heart attacks and strokes. We seek to understand how such oxyradicals are produced in the cells that make up the artery wall. Using novel DNA-type molecules we have recently discovered that a protein called Nox4 is ....In Australia, coronary heart disease (CHD) leading to heart attacks or strokes is 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, appears to be an important cause of CHD, heart attacks and strokes. We seek to understand how such oxyradicals are produced in the cells that make up the artery wall. Using novel DNA-type molecules we have recently discovered that a protein called Nox4 is crucial for the production of oxygen free radicals by blood vessels. Furthermore, we have identified a class of drugs that selectively block the activity of Nox4 in blood vessels. We now wish to directly test whether inhibiting Nox4, either with DNA-type molecules, various drugs known to block Nox4, or by complete elimination of the Nox4 gene in mice, prevents the development of CHD in animal models. This work will not only advance our understanding of the origin of vascular oxidative damage but will also allow us to identify novel therapeutic targets in the treatment of cardiovascular diseases that are associated with increased oxidative stress. The same drugs and molecules might also prove useful for improving recovery from heart attacks and strokes, for Nox4 may be turned on in the heart and brain in these conditions. Information obtained in our study will be useful in directing future prescription practices in clinical management of CHD and stroke, and for designing new therapeutic compounds for CHD.Read moreRead less
According to current National Heart Foundation surveys high blood pressure affects almost 3 million Australians, and accounts for about 6% of the total burden of disease. Unless effectively treated, high blood pressure may result in serious complications such as stroke, heart attacks and heart failure. Despite the fact that there are now many effective blood pressure-lowering medications available, blood pressure control in the community is often poor. The cause of high blood pressure in most pe ....According to current National Heart Foundation surveys high blood pressure affects almost 3 million Australians, and accounts for about 6% of the total burden of disease. Unless effectively treated, high blood pressure may result in serious complications such as stroke, heart attacks and heart failure. Despite the fact that there are now many effective blood pressure-lowering medications available, blood pressure control in the community is often poor. The cause of high blood pressure in most people is unknown, but there is consistent information from population studies that low vitamin C intake is associated with high blood pressure. Recently, it has been shown that a diet rich in fruit and vegetables can lower blood pressure. We recently demonstrated in a small study that vitamin C tablets for one month lowered blood pressure, suggesting that vitamin C was the key beneficial element of the fruit and vegetable diet. Interestingly, some recent work suggests that the recommended daily allowances of vitamin C are less than a third of what they need to be to get effective levels of vitamin C in body tissues. Studies in animal models of high blood pressure have shown that oxidant levels are increased. This can affect the ability of blood vessels to relax, and may be a cause, rather than a result of high blood pressure. It seems possible that vitamin C (a strong antioxidant) may be having its beneficial effect by reducing 'oxidant stress' in blood and blood vessel walls. The purpose of this project is to further determine the effect of oxidants and antioxidants (specifically vitamin C) on blood pressure and blood vessel function in patients with high blood pressure. It is clearly prudent to eat a diet rich in fruit and vegetables, but it is important that we understand why this is so, and whether specific dietary components are critical. Vitamin C might potentially make a major impact on the presence and severity of high blood pressure in the Australian community.Read moreRead less
Cardiovascular Reactivity To Stress: Role Of Redox Signalling In The Hypothalamus And Brainstem
Funder
National Health and Medical Research Council
Funding Amount
$606,979.00
Summary
Cardiovascular disease is Australia's greatest health problem. It kills more people than any other disease and affected 3.5 million Australians in 2004-05. More and more evidence suggests a relationship between the risk of cardiovascular disease and mental stress. But more research is needed on how stress contributes to heart disease risk. This project aims to determine the role of harmful molecules, called free oxygen radicals, in brain in mediating effects of stress on cardiovascular system.
Influence Of Superoxide On The Central Cardiovascular Response To Emotional Stress: Cellular And Subcellular Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$642,599.00
Summary
Cardiovascular disease is Australia's greatest health problem. It kills more people than any other disease and affected 3.5 million Australians in 2004-05. More and more evidence suggests a relationship between the risk of cardiovascular disease and mental stress. But more research is needed on how stress contributes to heart disease risk. This project aims to determine the role of harmful molecules, called free oxygen radicals, in brain in mediating effects of stress on cardiovascular system.