Increased serum angiopoietin-2 is associated with abdominal aortic aneurysm prevalence and cardiovascular mortality in older men.
ABSTRACT BACKGROUND: Angiopoietin-2 (Angpt2) has been implicated in the mediation and regulation of angiogenesis and inflammation which are believed to be critical mechanisms in the pathogenesis of both abdominal aortic aneurysm (AAA) and cardiovascular events. The aim of this study was to assess whether serum Angpt2 was associated with the prevalence of AAA and the occurrence of cardiovascular mortality in older men. METHODS: A cohort of 997 elderly men was recruited in 1996-99. Aortic ultrasound identified an AAA in 308 (31%). In 2001-04, blood was collected and serum Angpt2 later measured by immunoassay. The association of Angpt2 with AAA was assessed using multiple regression analysis. All men were followed by means of the Western Australia Data Linkage System until July 31st 2009. The association of Angpt2 with cardiovascular mortality was assessed using Cox proportional hazard analysis. RESULTS: Median serum Angpt2 was significantly higher (3.16ng/ml, inter-quartile range 2.51-4.54) in men with AAA compared with men without AAA (2.70ng/ml, inter-quartile range 2.03-3.72; p<0.001). After adjusting for cardiovascular risk factors, men with serum Angpt2 in the highest quartile (>3.95ng/ml) had a 2.57-fold (95% CI 1.66-3.97, p<0.001) increased odds of AAA and a 4.12-fold (95% CI 1.90-8.94, p<0.001) increased relative risk of cardiovascular mortality compared to men with serum Angpt2 in the lowest quartile (<2.13ng/ml). CONCLUSIONS: Serum Angpt2 is elevated in men with AAA and associated with an increased risk of cardiovascular mortality in older men.
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ABSTRACT: To determine the degree of neovascularisation in the wall of abdominal aortic aneurysms in comparison to atherosclerotic control aortas, and to correlate the angiogenic response with the extent of the cellular inflammatory infiltrate. Histopathological study. Aortic samples were obtained from patients with abdominal aortic aneurysms and from atherosclerotic controls. Samples were stained with haematoxylin and eosin, and Miller's elastin and Van Gieson stain, EVG, and a monoclonal antibody specific to human endothelial cells. Within the aortic wall three histological regions were defined, the media, the adventitia and a transition zone. The number of capillary like, thin walled vessels were measured in each region, and the cellular infiltrate was quantified. The number of newly formed vessels was increased in all layers of aneurysmal wall in comparison to control samples (p<0.001). The degree of neovascularisation correlated with the extent of the inflammatory infiltrate (rs=0.45, p<0.01). This study demonstrated that abdominal aortic aneurysms are associated with a marked angiogenic response, which is related to the degree of inflammation within the aortic wall. It is hypothesised that anti-angiogenic agents may play a role in the medical management of aortic aneurysmal disease.European Journal of Vascular and Endovascular Surgery 05/1996; 11(4):464-9. · 2.82 Impact Factor
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ABSTRACT: Angiogenesis is thought to depend on a precise balance of positive and negative regulation. Angiopoietin-1 (Ang1) is an angiogenic factor that signals through the endothelial cell-specific Tie2 receptor tyrosine kinase. Like vascular endothelial growth factor, Ang1 is essential for normal vascular development in the mouse. An Ang1 relative, termed angiopoietin-2 (Ang2), was identified by homology screening and shown to be a naturally occurring antagonist for Ang1 and Tie2. Transgenic overexpression of Ang2 disrupts blood vessel formation in the mouse embryo. In adult mice and humans, Ang2 is expressed only at sites of vascular remodeling. Natural antagonists for vertebrate receptor tyrosine kinases are atypical; thus, the discovery of a negative regulator acting on Tie2 emphasizes the need for exquisite regulation of this angiogenic receptor system.Science 08/1997; 277(5322):55-60. · 31.03 Impact Factor
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ABSTRACT: To evaluate the extent of neovascularisation in abdominal aortic aneurysms, specimens from the aneurysm walls of 17 consecutive patients (14 men, mean age 69 years, range 59 to 79 years) were studied and compared with specimens from patients with aortoiliac occlusive disease (n = 8, five men, mean age 53 years; range 40 to 71 years). Routine histology was performed after haematoxylin and eosin, Verhoeff's elastic and periodic acid-Schiff stainings. For immunophenotypic analysis of inflammatory cells four monoclonal mouse antibodies (UCHL1, L26, PG-M1 and KP1) were used. The histological sections through the walls of the AAAs showed extensive destruction of elastin and variable inflammation. Dense neovascularisation was seen throughout the aortic wall in the AAA cases compared to a mild angiogenetic response seen only occasionally in the AODs. Angiogenesis may play a significant role in the AAA process by recruiting and carrying a macrophage-rich infiltrate to the aortic wall.Annales chirurgiae et gynaecologiae 02/1998; 87(1):40-2.