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Title: TNF-related apoptosis-inducing ligand in abdominal aortic aneurysms
Author: Liu, Xun
Awarding Body: University of Bath
Current Institution: University of Bath
Date of Award: 2006
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Abdominal aortic aneurysm (AAA) is a progressive weakening of the aortic wall commonly associated with vascular calcification. Human AAA tissue displays cells undergoing all stages of apoptosis. It is known that aortic medial layer thinning, leads to aneurysmal formation through loss of aortic wall tone and increased wall stresses. Medial layer thinning is also associated with a decrease in smooth muscle cell (SMC) numbers. The cause of this loss of SMCs is attributed to apoptosis. Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is capable of inducing apoptosis in transgenic cells from various disease states but not in normal cells. An inhibitor of TRAIL, osteoprotegerin (OPG), is involved in osteoporosis and vascular calcification. We wished to investigate this link between vascular calcification and apoptosis by examining TRAIL and its receptors in AAA. Both qualitative and quantitative analysis of calcification in AAA walls was determined using Von Kossa staining and pre-operation computer tomography (CT) scans. Apoptosis in human AAA sections was confirmed by TUNEL assay and detection of apoptosis cellular marker by histology staining. Protein blots and RT-PCR were carried out to investigate the expression of TRAIL and its receptors in AAA walls. Comparative analysis was performed between normal aortae and AAA. A significant difference was observed between normal aortae and AAA for death receptor TRAIL-R2 mRNA (decreasing in AAA, p < 0.01) and OPG protein (decreasing in AAA, p<0.01). Significant differences were also observed between tissues displaying different extents of calcification for TRAIL mRNA (increases while the calcification level increseas; p<0.05). To mimic the AAA development models, AAA specimens were dissected into three different areas according to the anatomy structure. This separation is also confirmed by CT scan and supported by blood flow diametric theory.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available