Development Of Abdominal Aneurysms Research Articles

High Heritability of Abdominal Aortic Aneurysms – A Population-based Twin-study

Introduction: It is well known that there is an increased risk of developing abdominal aneurysms (AAA) among first-degree relatives of AAA-patients; however, it is still uncertain how great a role genetics generally play in the development of the disease. In twin studies the influence of genetic and environmental factors can be assessed by comparing concordance rates between monozygotic (MZ) and dizygotic (DZ) twins. Higher phenotypic similarity between MZ than DZ twins indicates a genetic attribution to the etiology. The primary aim of this study was to investigate the heritability of AAA among Danish twins using concordance rates and heritability estimates. Secondary aims were to investigate possible differences between gender regarding age at diagnosis and prevalence. Methods: We identified all Danish twins with AAA using three different population-based registries: the National Hospital Patient Registry, the Registry of Cause of Death and the Danish Twin Registry, which were linked together using the Danish Civil Registration System. We calculated age at diagnosis and prevalence for both men and women, and proband-wise concordance rates. Heritability was estimated using tetrachoric correlations and structural ADCE-modelling. Results: We included 65 –820 twins (32 –910 pairs). We identified 414 twins with AAA; 69.8 % (289/414) were men and 30.2 % (125/414) women. Mean age at diagnosis was 69.7 years with no significant difference between men and women (69.6 vs. 70.0 years, p = 0.64). The prevalence across all zygosities was 0.87% in men and 0.39% in women. The proband-wise concordance rate in MZ twins was 30.6% (95% CI (confidence interval):20.3;43.3%) compared with 12.2% (95%CI:7.0;20.1%) in DZ twins. In the analysis of heritability 77% (95%CI:67;85%) of the total variance could be explained by additive genetic components. The rest of the variance could be explained by non-shared environmental factors, whereas genetic dominance and shared environmental factors were not needed to account for the observed variance. Conclusion: In this study we found more than a two times higher concordance rate in MZ twins compared with DZ twins, which indicates a genetic component in the development of AAA. Furthermore we found an overall heritability of 77 % meaning genetic variance accounts for more than ¾ of the total phenotypic variance. Prevalences were generally low with women accounting for about a third of the AAA-cases and we found no difference between genders regarding age at diagnosis.

On constitutive descriptors of the biaxial mechanical behaviour of human abdominal aorta and aneurysms

The abdominal aorta (AA) in older individuals can develop an aneurysm, which is of increasing concern in our ageing population. The structural integrity of the ageing aortic wall, and hence aneurysm, depends primarily on effective elastin and multiple families of oriented collagen fibres. In this paper, we show that a structurally motivated phenomenological 'four-fibre family' constitutive relation captures the biaxial mechanical behaviour of both the human AA, from ages less than 30 to over 60, and abdominal aortic aneurysms. Moreover, combining the statistical technique known as non-parametric bootstrap with a modal clustering method provides improved confidence intervals for estimated best-fit values of the eight associated constitutive parameters. It is suggested that this constitutive relation captures the well-known loss of structural integrity of elastic fibres owing to ageing and the development of abdominal aneurysms, and that it provides important insight needed to construct growth and remodelling models for aneurysms, which in turn promise to improve our ability to predict disease progression.

Assessment of macrophage infiltration in a Murine model of abdominal aortic aneurysm

To evaluate the use of an ultrasmall superparamagnetic iron oxide (USPIO) contrast agent as a marker for the detection of macrophage in a preclinical abdominal aortic aneurysm animal (AAA) model. Osmotic pumps were implanted subcutaneously in apoE(-/-) mice for continuous infusion of Angiotensin II (Ang-II). Weekly bright-blood gradient echo scans were performed on the suprarenal abdominal aorta to evaluate aneurysm development. Once an AAA was detected, animals were administered 1000 mumol/kg of the USPIO contrast agent ferumoxtran-10 (Combidex) followed by in vivo scanning 24 h post-USPIO administration. After in vivo imaging, aortas were harvested for ex vivo imaging, histology, iron quantification, and gene expression analysis. Reduced signal intensity was evident in the post-USPIO transverse images of the abdominal aorta. The areas of reduced signal were primarily along the aneurysm shoulder and outer perianeurysm areas and corresponded to regions of macrophage infiltration and colocalized USPIO determination by means of histological staining. The absolute iron content measured significantly correlated to the area of signal reduction in the ex vivo images (r = 0.9; P < 0.01). In the AAA tissue, the macrophage-driven cytokine gene expression was up-regulated along with a matrix metalloproteinase known to mediate extracellular matrix breakdown in this disease model. These results demonstrate the feasibility of using an USPIO contrast agent as a surrogate for detecting the acute inflammatory process involved in the development of abdominal aneurysms.