Influence Of Flavonoid Structure And Function On Cardiovascular Protection
Funder
National Health and Medical Research Council
Funding Amount
$571,447.00
Summary
The proposed research will further explore the hypothesis that dietary flavonoids can protect against cardiovascular disease. The importance of flavonoid structure for bioactivity needs further study. In addition, metabolic changes to flavonoid structure could have a profound effect on their bioactivity. Therefore, our overall aim is to investigate the effects of individual flavonoids and their metabolites on bioactivity relevant to cardiovascular disease.
Vascular Effects Of Exercise Training And Lipid-lowering Therapy At Rest And During Exercise In Hypercholesterolaemia
Funder
National Health and Medical Research Council
Funding Amount
$241,650.00
Summary
The health of the cells which line blood vessels, endothelial cells, is now known to be important in maintaining normal function of the circulation. In patients with elevated blood cholesterol concentration, the function of these cells is abnormal and this is considered to contribute importantly to the blood vessel dysfunction and cardiovascular disease seen in this condition. We have recently demonstrated that drug therapy aimed at decreasing cholesterol concentration in the blood can significa ....The health of the cells which line blood vessels, endothelial cells, is now known to be important in maintaining normal function of the circulation. In patients with elevated blood cholesterol concentration, the function of these cells is abnormal and this is considered to contribute importantly to the blood vessel dysfunction and cardiovascular disease seen in this condition. We have recently demonstrated that drug therapy aimed at decreasing cholesterol concentration in the blood can significantly improve blood vessel function. In other studies we have demonstrated that exercise training improves blood vessel function. The purpose of this research is to determine whether high blood cholesterol impairs exercise capacity by limiting blood flow to exercising muscle. It is also our goal to determine whether exercise training can produce benefit additional to that resulting from lowering cholesterol in those with initially high cholesterol. Blood vessel function will be studied at rest, in response to pharmacological stimulation and during exercise. Vascular function in the forearm will be assessed using synchronised ultrasound (high frequency sound, sonar) and Doppler measures which assess the size of, and flow in, the large artery near the elbow crease. During measurements, procedures are undertaken to alter flow in the arm blood vessels, some depending upon functional ability of the endothelial cells and some independent of those cells. In addition to assessment of blood vessel function, measurements of exercise tolerance will be taken before and after each intervention. By examining the effects of lipid-lowering and exercise training on rest and exercise blood flow responses, this research will help determine the best approach to improving blood vessel function and cardiovascular fitness in patients with high cholesterol.Read moreRead less
Role Of Epigenetic Mechanisms In Diabetic Vascular Complications
Funder
National Health and Medical Research Council
Funding Amount
$438,520.00
Summary
Diabetic complications including heart attacks, strokes, kidney disease and blindness appear to be related to the high glucose (sugar) level but how glucose itself induces end-organ injury remains to be fully determined. In this proposal it is suggested that the long-term damaging effects of glucose relate to its ability to damage the regulation of genes by directly affecting DNA and its covering known as histones. Specifically glucose, possibly by altering certain biochemical pathways called ox ....Diabetic complications including heart attacks, strokes, kidney disease and blindness appear to be related to the high glucose (sugar) level but how glucose itself induces end-organ injury remains to be fully determined. In this proposal it is suggested that the long-term damaging effects of glucose relate to its ability to damage the regulation of genes by directly affecting DNA and its covering known as histones. Specifically glucose, possibly by altering certain biochemical pathways called oxidation pathways, interferes with enzymes which affect the structure of DNA and related molecules resulting in altered expression of many proteins. One of these proteins known as NF kappa B is activated in diabetes, probably by mechanisms involving regulation of these enzymes which play a central role in modifying gene structure. By clarifying the exact mechanisms at a molecular level that mediate the effect of glucose on genes and proteins it will be possible to target these molecules and develop new treatments to prevent, retard or reverse the blood vessel complications that are so common in diabetes.Read moreRead less
Role Of Chromatin Remodelling In Diabetic Renal And Vascular Complications: In Vivo Studies
Funder
National Health and Medical Research Council
Funding Amount
$474,618.00
Summary
Even after diabetics return to improved blood glucose levels after a period of poor blood glucose control, the kidney and blood vessel complications progress. The cause of this metabolic memory remains unexplained. This proposal focuses on sustained changes as a result of prior glucose levels in proteins called histones that are part of the wrapping of DNA. Using a new technique called carrier ChIP we will study histone modifications in the blood vessels and kidneys in diabetes.
Does Adenotonsillectomy Change Vascular Function In Children With Sleep Breathing Disorders?
Funder
National Health and Medical Research Council
Funding Amount
$522,105.00
Summary
Sleep breathing disorders affect 10% of all children and when severe, obstruction in the upper airways causes serious deficits in growth, development, brain function and heart health. But even mild snoring (without obstruction) may also cause poor health in the arteries that supply blood to the brain and heart, as well as the smaller arteries in the arms and legs. In both adults and children with conditions like diabetes and obesity, poor blood vessel health has been shown to greatly increase th ....Sleep breathing disorders affect 10% of all children and when severe, obstruction in the upper airways causes serious deficits in growth, development, brain function and heart health. But even mild snoring (without obstruction) may also cause poor health in the arteries that supply blood to the brain and heart, as well as the smaller arteries in the arms and legs. In both adults and children with conditions like diabetes and obesity, poor blood vessel health has been shown to greatly increase the future risk of heart attacks, angina and strokes. Children with severe sleep breathing disorders (such as sleep apnoea syndrome) are currently treated by removal of the tonsils and adenoids, which typically resolves snoring and improves sleep, but it is not yet known whether there are any benefits for blood vessel health. The earliest signs of blood vessel disease in children are abnormal function of the lining of the blood vessels (endothelial dysfunction) and thickening of the lining of blood vessels (intima media thickness). They precede the adult diseases of atherosclerosis - which causes heart attacks and strokes, and diabetic kidney and eye disease. These changes can be measured accurately and non-invasively using ultrasound imaging of arteries in the neck and arm. Our primary aim is to assess whether changes in blood vessel health occur in children with sleep breathing disorders across the range of severity, with a secondary aim to measure any changes in cardiovascular control during both sleep (when snoring occurs). Most importantly, by assessing children before and after surgery, we will be able to see for the first time whether treatment of childhood snoring improves blood vessel health. This study may have major implications for the clinical management of snoring children, who may require treatment at an earlier age to prevent poor blood vessel health and an increased risk of cardiovascular diseases later in life.Read moreRead less
(a) Pathogenesis Of Aortic Stenosis : Relationship To Valvular Endothelial Function.
Funder
National Health and Medical Research Council
Funding Amount
$254,995.00
Summary
In the 21st century, heart disease will continue to be a major cause of disability and death in Western society. However, the relative decline in the frequency of premature death due to coronary disease (such as heart attacks) combined with increases in longevity, will see the emergence of new disease states. Aortic stenosis (AS) is likely to be one of the most important of these: progressive aortic valvular narrowing, culminating in the development of heart failure, and cardiac death. To date, ....In the 21st century, heart disease will continue to be a major cause of disability and death in Western society. However, the relative decline in the frequency of premature death due to coronary disease (such as heart attacks) combined with increases in longevity, will see the emergence of new disease states. Aortic stenosis (AS) is likely to be one of the most important of these: progressive aortic valvular narrowing, culminating in the development of heart failure, and cardiac death. To date, the only established treatment for severe AS is valve replacement. The incidence of AS increases with age: approximately 40% of individuals over the age of 80 have some AS, while 4% have severe AS. Studies to date have revealed that AS is more likely to occur (and to progress rapidly) in patients with impaired kidney function, and that some coronary risk factors (high cholesterol levels and diabetes, for example) also predispose to AS. The planned research will examine the potential role of the (endothelial) cells lining the aortic valve in protecting against the development of AS. In particular, we will try to identify which chemicals interfere with endothelial function, and how this leads to thickening of the valve. The ulitmate objective of this research is to delineate the chemical factors causing AS, in order to help in the development of preventative strategies for this disease.Read moreRead less
Pharmacological Effects Of Oral L-citrulline And Tetrahydrobiopterin In Patients With Peripheral Artery Disease
Funder
National Health and Medical Research Council
Funding Amount
$322,283.00
Summary
Citrulline, named after citrullus vulgaris, the watermelon, is a precursor of arginine. Arginine is converted to protective nitric oxide (NO), which is decreased in cardiovascular diseases (CVD). Although arginine supplementation can increase NO availability and improve vascular function it is hampered by a low availability. In contrast, Citrulline is highly available and converted to Arginine. Therefore, this project will explore the therapeutic effects of Citrulline in patients with CVD.
Hypertension And Oxidative Stress: Effects Of Antioxidants On Blood Pressure, Endothelial Function And Oxidative Stress
Funder
National Health and Medical Research Council
Funding Amount
$329,122.00
Summary
Cardiovascular disease (CVD) is one of the most common causes of mortality in Western countries. Hypertension (raised blood pressure) is a major risk factor for CVD, and growing evidence suggests that oxidative stress contributes to raised blood pressure. Oxidative stress occurs when the body's antioxidant defences cannot prevent damage caused by free radicals (oxidants). Free radical damage may lead to impairment of blood vessel function resulting in raised blood pressure. Therefore, we will te ....Cardiovascular disease (CVD) is one of the most common causes of mortality in Western countries. Hypertension (raised blood pressure) is a major risk factor for CVD, and growing evidence suggests that oxidative stress contributes to raised blood pressure. Oxidative stress occurs when the body's antioxidant defences cannot prevent damage caused by free radicals (oxidants). Free radical damage may lead to impairment of blood vessel function resulting in raised blood pressure. Therefore, we will test the hypothesis that hypertension is associated with increased oxidative stress, and that dietary supplementation with water-soluble antioxidants will reduce oxidative stress, improve blood vessel function and lower blood pressure in hypertensives subjects with higher risk of CVD. To date, there is little direct evidence demonstrating that hypertension per se is associated with increased oxidative stress. Therefore, we will undertake a comparison where oxidative stress status will be assessed and compared in hypertensive subjects with and without other risk factors for cardiovascular disease and in normal healthy subjects. If oxidative stress were contributing to high blood pressure then dietary antioxidants would be expected to lower blood pressure in subjects with hypertension. Reduced oxidative stress and improved blood vessel function would also be expected with antioxidant supplementation. Results of population and intervention studies in humans suggest that vitamin C and other water-soluble antioxidants may reduce oxidative stress, improve blood vessel function and lower blood pressure. Therefore, we will study the effects of dietary supplementation with water-soluble antioxidants, including vitamin C and polyphenolic compounds (plant food-derived antioxidants) on these three main endpoints. We will also investigate whether the form in which the antioxidants are provided, tablets versus fruit juice drink, influences the effects observed.Read moreRead less