Smoking and Abdominal Aortic Aneurysm

Abdelkader Moussa (2011). Smoking and Abdominal Aortic Aneurysm MPhil Thesis, School of Medicine, The University of Queensland.

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Author Abdelkader Moussa
Thesis Title Smoking and Abdominal Aortic Aneurysm
School, Centre or Institute School of Medicine
Institution The University of Queensland
Publication date 2011-09-01
Thesis type MPhil Thesis
Supervisor Prof Malcom West
Dr Maria Nataatmadja
Dr Philp Walker
Total pages 99
Total colour pages 4( 32,43,39,46)
Total black and white pages 95
Subjects 11 Medical and Health Sciences
Abstract/Summary ix Abstract Abdominal aortic aneurysm (AAA) is an increasingly common vascular disease affecting 2-9% of elderly people aged more than 65 years. At the histopathological level AAA is characterized by pronounced changes affecting all three layers of the aortic wall. One of the most striking changes is the destruction of elastic lamellae in the tunica media. The breakdown of matrix components in the aortic wall of AAA has been attributed to increased activity of several metalloproteinases (MMPs): MMP-2, -3, -9, -12, and elastase. Vascular smooth muscle cell (VSMC) apoptosis is also believed to play a major role in AAA pathogenesis. Smoking has been considered an important risk factor associated with AAA development the pathophysiological mechanisms which underly its adverse effects are uncertain. In this thesis the effect of smoking on abdominal aortic wall structure in subjects with AAA was examined. Subjects with AAA who were smokers, ex-smokers or non smokers were recruited to the study at the time of AAA surgical repair and were compared with subjects without AAA who acted as controls. Histology, immunohistochemistry and immunoassay methods were used to determine the effect of smoking on the distribution of elastic lamellae in the tunica media, VSMC density and macrophage (MCPG) infiltration in the aortic wall. Plasma levels of MMP-2, MMP-9 and elastase were also measured. Histological analysis showed a significant (P<0.05) decrease in the number of elastic lamellae in AAA subjects compared to control subjects. The most severe reduction in elastin content was observed in AAA smokers (8 + 3 lamellae) compared to AAA ex- smokers (15 + 7 lamellae), AAA non smokers (18 + 3) and controls (39 + 4). On immunohistochemical examination there was increased macrophage infiltration in the media and adventitia of the aortic wall of AAA subjects (media: 7 + 3, adventitia: 8 + 2) compared to controls (media: 0, adventitia: 0). There was a decreased number of VSMCs in AAA cases compared to controls with the most severe reduction observed among AAA smokers (78%) compared to AAA ex-smokers (50%), AAA non smokers (50%) and controls. There was also an increase in MMP-12 expression x 3), AAA non smokers (4 + 1) and controls (1 + 1). x and activity in theaortic tissue of AAAgroups compared to controls. In AAAsmokers aortic tissue showed increased MMP-12 expression (11 +6 arbitrary units)compared to AAA ex-smokers (5 + 3), AAA non smokers (4 +1)and controls (1 +1). Immunoassayresults showed a significant increase in plasma level of MMP-2 in subjects with AAA (smokers: 50 +3, ex-smokers: 35 +1, non smokers: 34 +1) compared to subjects without AAA(smokers: 26 +1, non smokers: 23+1). PlasmaMMP-9 levels were also significantly increased in those with AAA (smokers: 42 +6,ex-smokers: 40 +8, non smokers: 45 +7) compared to subjects without AAA(smokers: 13 +3, non smokers: 10 +2). Howeverplasma elastase levels were notsignificantly different between those with and without AAA. My investigations confirm previouslyreported AAA pathological characteristicsnamely a decrease in number of elastic lamellae, increased macrophage infiltration,decrease in VSMC density and increase of activity of proteases(MMP-2, MMP-9,MMP-12 and elastase). However when aneurysm tissues were examined according to smoking statusI found that cigarette smoking was associated with an increasingdegree of elastin breakdown, macrophage infiltration and extent of MMP-12 activityin the aortic wall as well as increased plasma MMP-2 and elastase levels. The resultssupport a direct relationship between the level of smoking and the extent of aneurysmaortic wall damage. HoweverI was unable to determine whether smoking played arole in the initiation ofAAA or whether smoking acted to cause an already existentaneurysm to enlarge more significantly or more quickly. Further studiesare needed to assess at what stage smoking is linked to AAA development.
Keyword aaa: abdominal aortic aneurysm, aaap: autoimmune aortic protein, apoe :apoliprotein e, Coll:Collagen:, dab: diaminobenzidine, eds4 :ehlers-danlos syndrome type IV, esm: ex-smoker, mcpg: macrophage, mmp metalloproteinase, od: optical density smc: smooth mu
Additional Notes 32,43,39,46

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Created: Thu, 20 Oct 2011, 00:41:37 EST by Abdelkader Moussa on behalf of Library - Information Access Service