Intrauterine Growth Restriction And Development Of The Peripheral And Coronary Vasculature
Funder
National Health and Medical Research Council
Funding Amount
$437,176.00
Summary
There have been no studies which have investigated the extent to which fetal substrate restriction and associated fetal growth restriction alter the expression of nerve growth factors which determine the extent of sympathetic innervation of the peripheral vasculature and the interaction of changes within the peripheral and coronary vasculature which may explain the association between fetal growth restriction and the emergence of cardiovascular disease and high blood pressure in later life. Thes ....There have been no studies which have investigated the extent to which fetal substrate restriction and associated fetal growth restriction alter the expression of nerve growth factors which determine the extent of sympathetic innervation of the peripheral vasculature and the interaction of changes within the peripheral and coronary vasculature which may explain the association between fetal growth restriction and the emergence of cardiovascular disease and high blood pressure in later life. These studies ill provide new insights into the lifelong cardiovascular sequelae of a suboptimal intrauterine environment.Read moreRead less
Characterisation Of MiRNAs That Regulate Vascular Leakage.
Funder
National Health and Medical Research Council
Funding Amount
$167,493.00
Summary
Vascular permeability or leak is a major problem in diseases such as cancer and in cardiovascular diseases . MicroRNAs (miRNAs) are small control genes that influence dveleopment and disease. We have identified a miRNA cluster in endothelial cells, the cells that line the blood vessels, that is important in the control of vascular leak. This project is focused on understanding the impact of these miRNAs in disease.
Human Muscle Stretch Reflexes: The Effects Of Stimulus Properties, Muscle State And Subject Intention
Funder
National Health and Medical Research Council
Funding Amount
$170,604.00
Summary
The best known muscle reflex is the tendon jerk, which is usually evoked by tapping the muscle tendon with a small hammer. This tap imposes a very rapid stretch on the muscle, which produces a stretch reflex. Different stretch responses, however, can be observed to slow or fast stretches, or to vibration of muscle. Normally, when the muscles of a relaxed person are stretched, no active response is observed. However, when the person is engaged in a task and contracting their muscles, then stretch ....The best known muscle reflex is the tendon jerk, which is usually evoked by tapping the muscle tendon with a small hammer. This tap imposes a very rapid stretch on the muscle, which produces a stretch reflex. Different stretch responses, however, can be observed to slow or fast stretches, or to vibration of muscle. Normally, when the muscles of a relaxed person are stretched, no active response is observed. However, when the person is engaged in a task and contracting their muscles, then stretch modulates the muscle activity such that an increase in contraction of the muscle opposes the stretch and defends the position of the joint against the external disturbance. This is the everyday situation in which stretch reflexes operate. Despite extensive investigation for over a hundred years, there is still no consensus among researchers about the behaviour of stretch reflexes nor about their role in the control of movement. Even the demarcation of reflex from voluntary muscle activity is not always certain. One of the outstanding features of stretch reflexes is the variability of their behaviour, which depends on the particular muscle involved, its level of contraction, the type of stretch and the task in which the person is engaged. This variability has made it difficult for researchers to determine the role of reflexes in the control of movement. In order to study stretch reflex behaviour in human subjects, we will measure the electrical activity of elbow muscles, the elbow position and the force generated at the joint under a variety of conditions. A series of five experiments will investigate specific unresolved issues such as the effect of subject intention on the modulation of muscle activity and how altered modulation of muscle activity may change the stiffness of our limbs. The objective of the experimental series is to fill in important gaps in the picture of the behaviour of the stretch reflex.Read moreRead less
Role Of Epigenomic Changes In Conferring Hyperglycemic Memory
Funder
National Health and Medical Research Council
Funding Amount
$636,146.00
Summary
The major burden of type I diabetes remains its vascular complications including diabetes-accelerated athersclerosis. Despite improved glucose control, diabetic individuals develop complications as a result of prior poor glycemic control. Although the development and progression of these diabetic complications is strongly associated with mean levels of glucose, recent studies suggest that the deleterious effects of early exposure to high levels of glucose persist for years even after treatment h ....The major burden of type I diabetes remains its vascular complications including diabetes-accelerated athersclerosis. Despite improved glucose control, diabetic individuals develop complications as a result of prior poor glycemic control. Although the development and progression of these diabetic complications is strongly associated with mean levels of glucose, recent studies suggest that the deleterious effects of early exposure to high levels of glucose persist for years even after treatment has returned glucose levels towards normal.Read moreRead less
Early Events In Arteriolar Remodeling: Adaptation To Prolonged Vasoconstriction
Funder
National Health and Medical Research Council
Funding Amount
$415,750.00
Summary
Small arteries, while acutely responding to their environment with changes in diameter to regulate local blood flow and pressure, also undergo structural adaptation or remodelling. These events occur over a range of time-frames and involve both non-genetically and genetically regulated events. Thus a contractile event, while initially decreasing vessel diameter, also activates longer time frame processes which can span from rearrangment of cellular junctions-contacts to overt structural changes ....Small arteries, while acutely responding to their environment with changes in diameter to regulate local blood flow and pressure, also undergo structural adaptation or remodelling. These events occur over a range of time-frames and involve both non-genetically and genetically regulated events. Thus a contractile event, while initially decreasing vessel diameter, also activates longer time frame processes which can span from rearrangment of cellular junctions-contacts to overt structural changes within the vessel wall (for example thickening of the muscle layer). These adaptive processes may enable the forces of contraction to be maintained without continued energy expenditure and damage to the vessel per se. However, they can also contribute to long-term alterations in the control of blood pressure and perhaps contribute to states of hypertension as well as other common vascular diseases. For these studies we will use arterioles, isolated by microsurgical techniques, together with sophisticated computer and video-based approaches. These techniques allow arterioles to be studied under controlled conditions and relevant biochemical measurements performed. We will also use a cell model where cultured cells will be studied after defined periods of mechanical stimulation (for example stretch). Cells will be probed using a novel microscopic technique (atomic force microscopy) which enables the cell membrane to be studied with respect to changes in composition as well as physical characteristics (for example stiffness). The studies are relevant to our understanding of the normal adaptive processes occurring within blood vessels to control blood flow and pressure. The studies are also of direct relevance to our understanding of common vascular disease states including hypertension, complications of diabetes and chronic inflammatory disorders.Read moreRead less