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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
Molecular Mechanisms Of Disease In The Collagen VI-related Muscular Dystrophies
Funder
National Health and Medical Research Council
Funding Amount
$519,715.00
Summary
The inherited muscular dystrophies are an important cause of disability in Australia. This project concentrates on the second most common group of congenital muscular dystrophies - those caused by mutations in collagen VI and its interacting partners. We will determine how mutations affect the structure of the protein and how the muscle is disrupted by the mutations. This work will open the way for research into potential therapies. We will also find new genes that cause muscular dystrophy.
Mast Cells - Bystanders Or Instigators Of Airway Remodelling In Asthma?
Funder
National Health and Medical Research Council
Funding Amount
$623,764.00
Summary
Current asthma treatments have little effect on changes to the breathing tubes in our lungs. The tubes are thickened and stiffer, with more muscle, blood vessels, matrix and mucus. We propose that a particular inflammatory cell, called a mast cell, causes these changes to the breathing tubes and we will find out how it does that. Thus this project will establish why and how the changes to the breathing tubes happen in asthma and reveal how best to target and reverse-prevent them in the future.