Oxidation Of Arterial Extracellular Matrix By Myeloperoxidase-derived Oxidants
Funder
National Health and Medical Research Council
Funding Amount
$183,266.00
Summary
It is well established that changes occur in the composition and nature of the extracellular matrix present in the artery wall during the development of atherosclerosis. The changes that occur in this matrix affect both the mechanical and physical properties of the arterial wall (e.g. its ability to cope with the high pressures genrated by the pumping of blood from the heart) and the adhesion of cells. It is well established that certain key cell types do not adhere well, or grow properly, on al ....It is well established that changes occur in the composition and nature of the extracellular matrix present in the artery wall during the development of atherosclerosis. The changes that occur in this matrix affect both the mechanical and physical properties of the arterial wall (e.g. its ability to cope with the high pressures genrated by the pumping of blood from the heart) and the adhesion of cells. It is well established that certain key cell types do not adhere well, or grow properly, on altered or damaged matrix and this can result in either the loss of key cell types from the artery wall (e.g. loss of endothelial cells) and - or the proliferation and invasion of cells from other sources (e.g. smooth muscle cell invasion into the intimal space). There is circumstantial evidence that some of these changes occur via the formation of oxidants by the heme enzyme myeloperoxidase which is released from activated white cells. In this study we will employ recently developed analytical techniques to examine the nature of the alterations that are present in atherosclerotic plaques in comparison to normal human artery samples, and investigate the mechanisms by which such alterations arise. We will seek evidence for, or against, the involvement of myeloperoxidase-derived oxidants in the observed changes using specific markers which we have developed for the presence of such damage. This information will allow the rational design of strategies to interfere with the progression of atherosclerosis, which is the major killer of Australians.Read moreRead less
Therapeutic Regulation Of Matrix Metabolism To Stabilise The Biomechanical Properties Of The Sclera In High Myopia
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Myopia (short-sightedness) is due to the eye being too long. It is a common refractive disorder, affecting some 25-30% of people in developed countries, and results in blurred distance vision. Most myopia is easily correctable with spectacles or contact lenses. However a small, but significant, group of individuals have excessively long eyes and extreme amounts of myopia. These enlarged eyes impose abnormal stresses on the structures inside, particularly affecting the retina which is the light s ....Myopia (short-sightedness) is due to the eye being too long. It is a common refractive disorder, affecting some 25-30% of people in developed countries, and results in blurred distance vision. Most myopia is easily correctable with spectacles or contact lenses. However a small, but significant, group of individuals have excessively long eyes and extreme amounts of myopia. These enlarged eyes impose abnormal stresses on the structures inside, particularly affecting the retina which is the light sensitive part of the eye. Any damage that occurs to the retina in these eyes is, at present, untreatable and irreversible and can result in blindness. In fact, myopia is the 2nd leading cause of blindness amongst adults of working age. In order for the eye to grow so large its white, outer coat (the sclera) must expand without allowing any leaks of the delicate structures and fluids inside. Although the sclera gets very thin as it expands, it has been shown that this process of expansion is not just due to stretching. Before any stretching can occur the biochemical structure of the sclera must change. A complex process, involving the synthesis of structural components and the activity of enzymes that breakdown these structural components, is at work in the sclera of eyes that are rapidly enlarging. The aim of this project is to intervene in the biochemical processes that have already been shown to be involved in excessive eye enlargement. We will use both therapeutic agents and innovative gene therapy techniques to reverse the biochemical changes that occur in the sclera of rapidly enlarging eyes. We predict that these therapies will result in a sclera that is more resistant to being stretched and an eye that has less pathology. The results from this study will provide us with potential therapeutic strategies for the treatment of eyes that are enlarging excessively, thereby giving us the opportunity of preventing blindness in a number of highly myopic individuals.Read moreRead less
Airway Smooth Muscle Contribution To Remodelling In Asthma.
Funder
National Health and Medical Research Council
Funding Amount
$211,320.00
Summary
Asthma is an airway disease that affects more than 10% of adults and 25% of children in Australia and in 1998 caused 675 deaths. The cost to the community is in excess of $720 million a year. The abnormality in asthma is not fully understood, however inflammation, changes to the structure of the airways and excessive airway narrowing are key factors. Inflammation and the allergic reactions which accompany asthma cause fluid to leak from tiny blood vessels in the lung. This fluid and the inflamma ....Asthma is an airway disease that affects more than 10% of adults and 25% of children in Australia and in 1998 caused 675 deaths. The cost to the community is in excess of $720 million a year. The abnormality in asthma is not fully understood, however inflammation, changes to the structure of the airways and excessive airway narrowing are key factors. Inflammation and the allergic reactions which accompany asthma cause fluid to leak from tiny blood vessels in the lung. This fluid and the inflammation are linked to changes in the airway which include structural protein deposition - breakdown and an overgrowth of the smooth muscle that lines the walls of the airway. Our work is focussed on understanding the relationship between the structural protein deposition - breakdown and excess muscle growth. We also hope to gain a better understanding of the way asthma treatments combat these changes in the asthmatic airways.Read moreRead less