These preliminary observations point to a potential link between high wall stress and accelerated metabolism in aortic aneurysm wall and warrant further large population-based studies.

Background: Since aortic diameter is the most significant risk factor for rupture, we sought to identify stress-dependent changes in gene expression to illuminate novel molecular processes in aneurysm rupture. Materials and Methods: We constructed finite element maps of abdominal computerized tomography scans (CTs) of seven abdominal aortic aneurysm (AAA) patients to map wall stress. Paired biopsies from high-and low-stress areas were collected at surgery using vascular landmarks as coordinates. Differential gene expression was evaluated by Illumina Array analysis, using the whole genome DNA-mediated, annealing, selection, extension, and ligation (DASL) gene chip (n = 3 paired samples). Conclusion:Lamin A/C protein is specifically increased in areas of high wall stress in AAA from patients, but is not increased on other vascular beds of aneurysm patients, suggesting that its elevation may be a compensatory response to the pathobiology leading to aneurysms.

Background Abnormal blood flow patterns can alter the material properties of the thoracic aorta via altered vascular biology and tissue biomechanics. In-vivo haemodynamic assessment of the aorta is yet to penetrate clinical practice due to our limited understanding of its effect on aortic wall properties. The decision for surgical treatment is based on size thresholds, limited to a single measurement of aortic diameter from routine imaging, although many aortic dissections (40–60%) occur below these size thresholds. This multi-centre study aims to assess the clinical utility of biomechanics principles in thoracic aortic aneurysm (TAA) risk rupture prediction using a substantial sample size. Methods Fifty-five patients undergoing surgery for root or ascending TAA were recruited from five cardiac centres. Bicuspid aortic valves and connective tissue disease were excluded from this study.Haemodynamic assessment Pre-operative 4-dimensional flow magnetic resonance imaging (4D-MRI) were conducted. Direct 4D-flow analysis and computational fluid dynamics (CFD) were performed creating detailed wall shear stress (WSS) maps across the whole aneurysms. Aortic wall assessment The aneurysmal aortic sample was obtained from surgery and subjected to region specific uniaxial failure tests in the circumferential and longitudinal directions, as well as delamination testing within the aortic media. Whole aneurysm histological characterisation was also conducted using computational pathology techniques. Blood flow, tissue mechanics and microstructural properties were used to develop a risk prediction model with assessment of elastin, collagen and smooth muscle cell composition, as well as failure strain assessment and dissection energy function. Results Outcomes of mechanical properties were: Young's Elastic Modulus as a measure of aortic stiffness (0.85 MPa ±0.69), as well as maximal tensile strength (0.49 MPa ± 0.36), which demonstrated reduced aortic wall strength in the outer curvature. This correlated with increased wall shear stress (WSS) (up to 10 Pa) and flow velocity (up to 43 l/min). Regions of abnormal flow and tissue mechanics correlated significantly with degraded medial microstructure (elastin abundance: 34 vs 66%; collagen abundance 26 vs 57%, p<0.05). Conclusions CFD modelling has the potential to provide a risk prediction of acute events in TAA beyond the current size classification, as validated by altered aortic tissue properties. Future longitudinal studies are warranted to validate this methods in moderately enlarging thoracic aortas. Flow, mechanical, histology properties Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): NIHR Imperial College BRC

Background:Since aortic diameter is the most significant risk factor for rupture, we sought to identify stress-dependent changes in gene expression to illuminate novel molecular processes in aneurysm rupture. Materials and Methods:We constructed finite element maps of abdominal computerized tomography scans (CTs) of seven abdominal aortic aneurysm (AAA) patients to map wall stress. Paired biopsies from high-and low-stress areas were collected at surgery using vascular landmarks as coordinates. Differential gene expression was evaluated by Illumina Array analysis, using the whole genome DNA-mediated, annealing, selection, extension, and ligation (DASL) gene chip (n = 3 paired samples). Results: The sole significant candidate from this analysis, Lamin A/C, was validated at the protein level, using western blotting. Lamin A/C expression in the inferior mesenteric vein (IMV) of AAA patients was compared to a control group and in aortic smooth muscle cells in culture in response to physiological pulsatile stretch. (962-2919 µm)]. Induced expression of Lamin A/C correlated with areas of high wall stress from AAAs but was not significantly induced in the IMV from AAA patients compared to controls (n = 16). Stress-induced expression of Lamin A/C was mimicked by exposing aortic smooth muscle cells to prolonged pulsatile stretch. Conclusion: Lamin A/C protein is specifically increased in areas of high wall stress in AAA from patients, but is not increased on other vascular beds of aneurysm patients, suggesting that its elevation may be a compensatory response to the pathobiology leading to aneurysms. Areas of high wall stress (n = 7) correlate to those regions which have the thinnest walls [778 µm (585-1120 µm)] in comparison to areas of lowest wall stress [1620 µm

We read with great interest the paper by Xu et al. where they demonstrated in a small series of aortic aneurysms that predicted peak wall stress (PWS) regions coincided with the region of high uptake of FDP, suggestive of a focally accelerated metabolism attributed to inflammatory changes affecting the structural integrity of aneurysm wall. 1 The authors suggest a potential causal relationship between high wall stress and accelerated metabolism.This study should be commended for being the first to investigate the possible conjugation of PWS sites with biochemical markers that have been proven to correlate with decreased wall strength. 2 The simultaneous combination of the latter with PWS could give a more reliable prediction of rupture risk.However, it should be noted that in these aortic aneurysms, the PWS sites were located at the junction between the neck and the sac, where little if any amount of thrombus was present. It is known that the presence of thrombus is associated with cellular inflammatory changes in the aneurysm wall 3 and local reduction of the wall strength. 4 So, in aneurysms with a thick layer of ILT, stress values would be considerably reduced at the thrombus sites, where at the same time, the induced inflammatory reaction would cause an elevated uptake of FDP, thus, the site with elevated FDP uptake may not correspond to the location of PWS.