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|Title: ||Molecular and Cellular Determinants of Neovascularisation and Vascular Repair|
|Authors: ||CHAN, Kim Hoe|
|Keywords: ||Cardiovascular disease; Haem oxygenase-1; Endothelial progenitor cell|
|Issue Date: ||9-Jan-2014|
|Publisher: ||University of Sydney, Heart Research Institute, Central Clinical School|
|Abstract: ||Cardiovascular disease remains the leading cause of death worldwide. However, there remain a significant number of patients who are not eligible for current treatment options. Therapeutic angiogenesis offer great potential in the treatment of cardiovascular disease. Recent experiments demonstrated that haem oxygenase-1 (Hmox1) possesses pro-angiogenic and atheroprotective properties. Recent studies have also shown that the vascular protective effects of Hmox1 may be mediated by endothelial progenitor cell (EPC) mobilisation. EPCs are implicated in vascular regeneration and angiogenesis. However, outcomes from clinical trials on cell therapy have been disappointing and hampered by the use of unselected cell populations.
This thesis therefore investigated several aspects of the role of Hmox1 and EPCs in therapeutic angiogenesis and vascular repair. Firstly, the role of Hmox1 in ischaemia-mediated neovascularisation was investigated. Secondly, the relationship between bilirubin concentration (a surrogate marker of Hmox1 activity in humans) and amputation was explored. Thirdly, the relationship between level and function of distinct EPC populations and coronary collateralisation, as well as the extent of coronary epicardial and microvascular disease, was explored.
There were several key findings from this thesis. Firstly, we found that Hmox1 played a critical role in ischaemia-mediated neovascularisation, and that this protective effect of Hmox1 may be mediated by EPC mobilisation and hypoxia-induced glucose metabolism. Secondly, we found an inverse relationship between bilirubin concentration and amputation. Lastly, we found that higher late-outgrowth endothelial cell, but not early EPC, levels and function were associated with better coronary collateralisation and less severe epicardial coronary disease. These findings may have implications for therapeutic angiogenesis and atheroprotection in the treatment of cardiovascular disease.|
|Access Level: ||Access is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.|
|Rights and Permissions: ||The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.|
|Type of Work: ||PhD Doctorate|
|Type of Publication: ||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (University of Sydney Access only)|
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|CHAN Kim Hoe - Final Thesis.pdf||3.42 MB||Adobe PDF|
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