Increased Expression of Lamin A/C Correlate with Regions of High Wall Stress in Abdominal Aortic Aneurysms.

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. -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 (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.

Treatment of a juxtarenal aneurysm with the Nellix endovascular aneurysm sealing system and chimney stent.

PURPOSE: To present treatment of a juxtarenal aneurysm using the Nellix endovascular aneurysm sealing system (EVAS) and a chimney stent. CASE REPORT: A 79-year-old woman was diagnosed with a 6-cm juxtarenal aneurysm. Standard endovascular aneurysm repair was not possible due to lack of an adequate infrarenal landing zone, and poor iliac access and angulated visceral aortic branches precluded a custom-made fenestrated solution. The patient was not a suitable candidate for open surgery due to significant comorbidity, so she underwent successful endovascular aneurysm repair with the Nellix EVAS system and a renal chimney stent. Follow-up imaging at 6 months showed a sealed aneurysm sac and patent renal chimney stent. CONCLUSION: The Nellix EVAS system obliterates the aneurysm sac using polymer-filled endobags. The ability of the endobags to conform to adjacent structures may offer advantages over conventional endografts when combined with parallel grafts designed to treat juxtarenal aneurysms.

Comparative proteomics reveals a systemic vulnerability in the vasculature of patients with abdominal aortic aneurysms.

INTRODUCTION: Abdominal aortic aneurysms (AAA) are associated with inflammation, apoptosis, and matrix degradation. AAA tissue represents the end stage of disease, limiting its utility in identification of factors culpable for initiation of aneurysm development. Recent evidence suggests that AAAs are a local representation of a systemic disease of the vasculature. Morphologic and molecular changes, comparable to those found in the aneurysm wall, have been demonstrated in veins from patients with AAAs. Changes in the vascular tissue proteome of patients with AAAs were investigated, using inferior mesenteric vein (IMV), to gain insight into early molecular changes contributing to AAA development. METHODS: IMV was harvested from 16 patients with AAA and 16 matched controls. Whole IMV lysates were subjected to 2-D difference in gel electrophoresis (2D-DIGE) with quantitative densitometry. Protein spots differentially expressed in AAA were identified using mass spectrometry. Differential protein expression was validated by Western blotting and localized to cell type by immunohistochemistry (IHC). RESULTS: Decreased levels of prohibitin (AAA, 2.00 ± 1.37; controls, 3.81 ± 1.39; 1.9-fold change; P = .02) AAA (7.33 ± 3.9; controls, 14.5 ± 5.6; 2-fold change; P = .001), along with relative increases in a cleaved fragment of vimentin (AAA, 12.9 ± 9; controls, 6.9 ± 4.7; 2-fold change; P = .11) were identified in AAA patients. All proteins were localized to the vascular smooth muscle cells. CONCLUSIONS: Proteins important in combating the injurious effects of oxidative stress and modulating the response to inflammation appear reduced in the vasculature of patients with AAA. These changes may represent early events in AAA formation. Enhancing expression of these proteins might offer a novel therapeutic avenue to inhibit AAA development.

Morphology of aortic arch pathology: implications for endovascular repair.

PURPOSE: To present a detailed description of aortic arch morphology in patients with aneurysm and dissection undergoing thoracic endovascular aortic repair (TEVAR). METHODS: Morphological assessment of the aortic arch was performed in a consecutive series of patients undergoing TEVAR between November 2003 and April 2009. In the absence of standardized reporting criteria, any patient requiring overstenting of the left subclavian artery (LSA) was considered to have pathology of the aortic arch. In all, the arch morphology of 49 patients (31 men; mean age 70 years, range 43-86) was analyzed (25 aneurysms and 24 dissections). The proximal landing site of the intended stent-graft was Ishimaru zone 0 in 2 (4%) patients, zone 1 in 11 (22%), and zone 2 in 36 (74%). Measurements were made of the aortic arch diameters and angulation and the orientation and diameters of the supra-aortic trunks from 3-dimensional reconstructions of computed tomography scans. RESULTS: The diameter of the aortic arch increased as it approached the aortic root (mean 38.9+/-6.4 mm at the sinotubular junction versus 30.7+/-16.6 mm at the left subclavian artery (LSA). Mean angulation of the arch at the level of the LSA was 117 degrees +/-23 degrees . Five (10%) patients had a common origin of the innominate artery and left common carotid artery (LCCA). The distance between the LCCA and the LSA was <15 mm in 80%; 37 (80%) had clock-face positions of the LCCA and LSA ostia within 15 degrees of each other. There was no statistical difference in any measurements between the aneurysm and dissection patients. CONCLUSION: In this cohort, morphology was similar for patients with aneurysm or dissection. The distance between the LCCA and the LSA in the majority of cases was shorter than the recommendation for an adequate proximal landing zone. This data may assist in the development of stent-grafts for the aortic arch.

Patient-specific biomechanical profiling in abdominal aortic aneurysm development and rupture.

INTRODUCTION: It is difficult to reliably predict abdominal aortic aneurysm (AAA) expansion and rupture in individuals. There is increasing interest in the role of patient-specific biomechanical profiling of AAA development and rupture. This review examines evidence to support the use of biomechanical profiling in AAA. METHODS: The literature was systematically reviewed to examine the evidence to support the role of patient-specific biomechanical profiles in the management of patients with AAA. A search of Medline, Medline in process and other nonindexed citations, and EMBASE was performed for articles published from January 1980 to December 2008. The search strategy retrieved 2410 titles. After exclusions, 83 articles were reviewed in full and form the basis of this review. RESULTS: There is increasing evidence that patient-specific biomechanical factors may be more reliable in predicting AAA rupture than currently available clinical and biochemical parameters. Wall stress determination using finite element analysis is consistently higher in symptomatic and ruptured AAA. Recent improvements in computational methodology and advances in imaging and processing technology have increased the power of these biomechanical factors in predicting AAA expansion and rupture. CONCLUSIONS: Major progress has been made in the development of biomechanical profiles for AAA. Large population-based studies for validation of patient-specific biomechanical profiles with rupture risk assessment and tailored decision making are now indicated, particularly with the introduction of AAA screening programs.

Morphological suitability of patients with aortoiliac aneurysms for endovascular preservation of the internal iliac artery using commercially available iliac branch graft devices.

PURPOSE: To quantify the proportion of patients with morphology suitable for the use of a commercially available iliac branch graft device (IBD), which offers an endovascular alternative to avoid the morbidity of internal iliac artery (IIA) embolization during endovascular aneurysm repair (EVAR) of aortoiliac aneurysms. METHODS: A retrospective single-center study was conducted of 51 patients (44 men; mean age 75+/-7 years) undergoing IIA embolization (36 unilateral, 15 bilateral) prior to EVAR between June 2005 and August 2009. Three-dimensional volume-rendered reconstructions of computed tomographic angiography (CTA) scans were compared to criteria published by experienced surgeons and to manufacturer's instructions for use (IFU). Morphological suitability for IBD was graded with a score reflecting 15 variables (morphological score) extracted from the IFU and publications from experienced endovascular centers. The higher the score, the more adverse morphological features were encountered. RESULTS: In the 51 patients, 66 target IIAs were studied. Of these, 25 (38%) target IIAs with a mean morphological score 4.44+/-1.96 were compliant with the manufacturer's IFU. Nineteen (29%) target IIA were compliant with experienced surgeons' criteria, with a mean morphological score of 4.2+/-2.0. The most common adverse feature was an aneurysmal IIA. CONCLUSION: In a population of patients with aortoiliac aneurysms, morphological applicability of a commercially available IBD was low, with the majority of patients possessing at least 1 adverse anatomical feature. A validated morphological scoring system derived from registry-type data is needed, with quantification of outcomes in IBD deployment that extends the IFU.

Validation of DynaCT in the morphological assessment of abdominal aortic aneurysm for endovascular repair.

PURPOSE: To evaluate the feasibility of intraoperative 3-dimensional rotational angiography (DynaCT) as a single tool to assess suitability for endovascular aneurysm repair (EVAR) and for sizing the stent-graft. METHODS: Twenty elective patients undergoing EVAR were prospectively recruited. All had preoperative multidetector computed tomography (CT) scans and intraoperative (pre-stent deployment) DynaCT scans. Images were read independently by 4 experienced endovascular practitioners. A total of 17 morphological variables, including aneurysm neck diameter and length, were measured from the CT and DynaCT images and compared. Bland-Altman plots examined intraclass correlation of continuous outcomes; kappa correlation coefficient assessed agreement of ordinal results. RESULTS: The mean DynaCT radiation dose was 3751+/-835 microGym(2). The mean difference between DynaCT and multidetector CT in aneurysm neck diameter measurement was -1.5 mm (95% CI -4.9 to 1.9). Differences in left and right common iliac artery diameters were -1.9 mm (95% CI -6.3 to 2.4) and -2.1 mm (95% CI -6.9 to 2.7), respectively. For presence of neck thrombus, the group kappa statistic was 0.51 (p<0.0001); for neck calcification, the kappa was 0.07 (p = 0.29). Nine (45%) cases had incomplete information on DynaCT because external iliac arteries were not included in the scan. CONCLUSION: DynaCT provides adequate preoperative imaging for morphological assessment of aortic anatomy. The greatest limitation is the evaluation of access vessels and underestimation of calcification. Due to current limited detector size, precise positioning is essential to attain all necessary sizing information using DynaCT.