OBJECTIVES:This study used the whole transcriptome approach to investigate the role of genes involved in immune and inflammatory response at the site of aneurysm rupture.MATERIALS AND METHODS:Rupture site and paired anterior sac biopsies (internal control) of ruptured abdominal aortic aneurysms (AAAs) (n=10) were analysed with Affymetrix Human Genome U133A plus 2.0 microarray. Twenty-one differentially expressed genes were selected for validation using quantitative reverse transcriptase polymerase chain reaction (QRT-PCR).RESULTS:A total of 139 genes (123 upregulated, 16 downregulated) at the aneurysm rupture site were differentially expressed (>2.5-fold, P<0.005). Immune and inflammatory responses (Gene Ontology Classification) were frequently associated with the differentially expressed genes. Genes with immune and inflammatory functions that were confirmed, by QRT-PCR, to be overexpressed at the aneurysm rupture site were interleukins-6 and -8 (IL-6 and -8), Selectin E (SELE), prostaglandin-endoperoxidase synthase 2 (COX2) and prokineticin 2 (PROK2). IL-6 (pro-immune) and IL-8 (pro-immune and pro-inflammatory) have previously been linked to aneurysm rupture; and SELE and COX2 (pro-inflammatory) have previous associations with aneurysm development but not rupture.CONCLUSIONS:The differential expression of genes involved in immune and inflammatory responses was confirmed at AAA rupture site. These genes may represent novel targets for treatment of aneurysms.

BACKGROUND:The role of matrix metalloproteinases (MMPs) in abdominal aortic aneurysm (AAA) formation is well established. However the changes in plasma MMP levels with AAA rupture have not been reported. The aim of this study was to determine circulating levels of MMPs in non-ruptured and ruptured AAA immediately prior to open repair.METHODS:Concentrations of MMPs and their endogenous tissue inhibitors (TIMPs) were quantified using ELISA in pre-operative plasma samples from non-ruptured and ruptured AAA.RESULTS:MMP1 and MMP9 were elevated in the plasma of ruptured AAA versus non-ruptured AAA. A four-fold elevation in pre-operative plasma MMP9 was associated with non-survival at 30 days from rupture surgery compared with those surviving for greater than 30 days.CONCLUSION:In conclusion, these findings support the role of MMPs in AAA pathogenesis. Elevation of MMP9 was associated with ruptured aneurysm related 30-day mortality and may represent a survival indicator in this group.

Objectives. Patients with aortic aneurysms have significant comorbidities which influence outcome. Our practice includes comprehensive assessment to identify comorbidities, allowing subsequent medical optimisation prior to aneurysm repair. The aim of this study was to assess this process and to identify any factors predictive of outcome.Design. Prospective observational study.Materials. Medical case notes of 200 patients referred with aortic pathology.Methods. Data analysed included preoperative, perioperative and postoperative factors. Multiple logistic regression analysis was performed to identify predictors of outcome.Results. Following assessment 17 patients (8.5%) were found to be unfit for intervention and 165 patients (82.5%) proceeded to aneurysm repair. In this group assessment uncovered previously undiagnosed cardiac, respiratory and renal comorbidity in 19%, 57% and 29% of patients respectively. Multiple logistic regression analysis indicated that optimisation by a renal physician reduced post-operative renal impairment (OR 0.12, 95% CI 0.03-0.45, P = 0.002) while optimisation by a cardiologist reduced respiratory complications (OR 0.7, 95% CI 0.05-0.99, P = 0.049). An abnormal echocardiogram was associated with pneumonia (OR 6.9, 95% CI 1.6-29, P = 0.01) and death (OR 7.9, 95% Cl 1.15-54, P = 0.036).Conclusion. Pre-operative assessment identifies previously undiagnosed comorbidity in a significant proportion of patients. Subsequent medical optimisation may reduce post-operative morbidity and mortality.

Objective: Abdominal aortic aneurysm (AAA) development is associated with increased angiogenesis and overexpression of vascular endothelial growth factor (VEGF). Inhibition of angiogenesis results in attenuation of experimental aneurysms. This study investigated the effects of recombinant human (rh)VEGF on experimental aneurysms.Methods: Apolipoprotein E-deficient (apoE(-/-)) mice were assigned to one of four groups: (1) normal saline infusion (sham), (2) angiotensin-II (AngII) infusion, (3) AngII infusion plus 100 mu g daily rhVEGF for 14 days (AngII + 14dVEGF), or (4) AngII infusion plus 100 mu g daily rhVEGF for 21 days (AngII + 21dVEGF). Aortic maximum diameter and cross-sectional area were determined by magnetic resonance imaging and microscopy. All mice were sacrificed at day 28.Results: Aneurysms developed in all mice in the AngII+14dVEGF and AngII+21dVEGF groups by day 21 compared with 40% in the AngII group. Treatment with rhVEGF increased maximum aortic diameter (P <.002) and crosssectional area of aneurysms (P <.005) at day 21. This effect was maintained at day 28 (P <.0005). Decreasing rhVEGF treatment from 21 to 14 days did not attenuate aneurysm formation. Treatment with rhVEGF upregulated matrix metalloproteinase 2 gene expression within the aortic wall (P <.0009).Conclusions: Treatment with rhVEGF intensified the formation of Angll-induced aneurysms. Further studies are needed to investigate if antiangiogenic therapy may be a valid medical therapy against aneurysm expansion or rupture. (J Vase Surg 2010;52:159-66.)

Abdominal aortic aneurysms (AAAs) principally affect men over 60 years of age. Aneurysms are usually asymptomatic and detected coincidentally or following the onset of symptoms. Elective repair of an AAA is considered when the diameter reaches 5.5cm or annual expansion exceeds 1cm. Rupture represents a catastrophic event and carries an unacceptably high mortality. The advent of endovascular repair heralds an improvement in operative outcome for this disease process. In this review we provide an overview of the recent trials investigating the management of non-ruptured and ruptured aneurysms and the strategies that may be invoked to lower the mortality of this disease process

To search for novel transcriptional pathways that are activated in abdominal aortic aneurysm rupture, cDNA microarrays were used to compare global mRNA expression at the aneurysm rupture edge to anterior sac, and selected results were confirmed using quantitative real-time-polymerase chain reaction (QRT-PCR). This study identified apoptosis, angiogenesis, and inflammation as potentially important participants during the process of aneurysm rupture.

Traditional open surgical repair for mycotic aneurysms of the thoracic aorta is associated with significant morbidity and mortality. Endovascular repair has been reported as an alternative treatment in patients with mycotic thoracic aneurysms. This article reports our experience of endovascular stent graft placement in three patients with mycotic aneurysms of the thoracic aorta and compares the results with similar reports on the literature.

Abdominal aortic aneurysm (AAA) rupture is the 13th commonest cause of death in the Western World. Although considerable research has been applied to the aetiology and mechanism of aneurysm expansion, little is known about the mechanism of rupture. Aneurysm rupture was historically considered to be a simple physical process that occurred when the aortic wall could no longer contain the haemodynamic stress of the circulation. However, AAAs do not conform to the law of Laplace and there is growing evidence that aneurysm rupture involves a complex series of biological changes in the aortic wall. This paper reviews the available data on patient variables associated with aneurysm rupture and presents the evidence implicating biological factors in AAA rupture.