Metformin Improves the Function of Abdominal Aortic Aneurysm Patient Derived Aortic Smooth Muscle Cells.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a cardiovascular risk factor. Paradoxically, a decreased risk of abdominal aortic aneurysm (AAA) presence and growth rate is described among patients with T2DM, associated with metformin use. This study aimed to investigate the effect of metformin on AAA patient derived aortic smooth muscle cell (SMC) function. METHODS: Aortic biopsies were obtained from patients with AAA (n = 21) and controls (n = 17) during surgery. The SMCs of non-pathological aortic controls, non-diabetic patients with AAA, and diabetic patients with AAA were cultured from explants and treated with or without metformin. The SMC contractility was measured upon ionomycin stimulation, as well as metabolic activity, proliferation, and migration. Then, mRNA and protein expression of markers for contraction, metabolic activity, proliferation, and inflammation were measured. RESULTS: The mRNA expression of KLF4 and GYS1, genes involved in metabolic activity, differed between the SMCs from non-diabetic and diabetic patients with AAA before metformin stimulation (p < .041). However, the effect of metformin on the various SMC functions was similar between non-diabetic and diabetic patients with AAA. Upon stimulation, metformin increased the contractility of AAA patient SMCs (p = .001). The mRNA expression of smoothelin, a marker for the contractile phenotype, increased in the SMCs of patients with AAA after treatment with metformin (p = .006). An increase in metabolic activity (p < .001) and a decrease in proliferation (p < .001) and migration were found in the SMCs of controls and patients with AAA with metformin. Increased mRNA expression of PPARγ, a nuclear receptor involved in mitochondrial biogenesis (p < .009), and a decrease in gene expression of Ki-67, a marker for proliferation (p < .005), were observed. Gene expression of inflammation markers MCP-1 and IL-6, and protein expression of NF-κB p65 decreased after treatment with metformin in patients with AAA. CONCLUSION: This study found that metformin increases contractility and metabolic activity, and reduces proliferation, migration, and inflammation in aortic SMCs in vitro.

What we have learned from in-vitro studies of the chimney endovascular technique for treatment of complex abdominal aortic aneurysms: A systematic review.

BACKGROUND: A considerable number of patients with abdominal aortic aneurysms (AAA) is not eligible for standard endovascular repair. These complex cases require alternative surgical approaches including the readily available chimney graft endovascular aneurysm repair (Ch-EVAR) or sealing (Ch-EVAS). The optimal configuration for Ch-EVAR or Ch-EVAS is important for success but not yet known. OBJECTIVE: The aim of the present study was to analyze current data of the outcomes of in-vitro chimney graft treatment in complex AAA. METHODS: A systematic review following PRISMA guidelines was conducted including studies reporting on gutter size, main graft compression, and chimney graft compression in in-vitro configurations. RESULTS: The search resulted in 285 articles. 11 studies considering 219 individual tests could be included. Gutter size was comparable between Ch-EVAR and Ch-EVAS configurations. In Ch-EVAR set-ups, the deployed BECG were Advanta V12, VIABAHN®, and BeGraft. One type of SECG was used: VIABAHN®. The four types of main grafts (MG) deployed were: Endurant™ I/II; EXCLUDER Conformable AAA Endoprosthesis and AAA Endoprosthesis, and AFX™ Endovascular AAA Delivery System. In the EVAS-configurations, the Nellix® EVAS system was deployed. In general, SECG presented smaller gutters with higher chimney graft compression. 30% main grafts oversizing seems to give the smallest gutters without high risk of infolding of MG. Oversizing, EndoAnchors, and secondary endobag filling (in Ch-EVAS) reduced gutter sizes. CG ballooning during the entire polymer injection in Ch-EVAS prevented CG compression. CONCLUSION: In-vitro investigations provide insight in optimal Ch-EVAR and Ch-EVAS configurations for simulated complex AAA repair. The findings above might aid physicians in their planning to potential CG set-ups and can be used in future research to refine the most optimal configuration for chimney graft technique in complex AAA.

Identifying high risk for proximal endograft failure after endovascular aneurysm repair in patients suitable for both open and endovascular elective aneurysm repair.

OBJECTIVE: Proximal endograft failure (type Ia endoleak or migration) after endovascular aneurysm repair (EVAR) is associated with hostile aneurysm neck morphology. Neck scoring systems were developed to predict proximal endograft failure but were studied in retrospective studies, which, due to selection bias, may have led to an overestimation of bad outcomes after EVAR. To predict patients who benefit from open repair, preoperative neck morphology and occurrence of long-term proximal endograft failure were investigated in patients enrolled in the endovascular arm of the Dutch Randomized Endovascular Aneurysm Management (DREAM) trial who were suitable for open repair by definition and have long-term follow-up. METHODS: A post-hoc on-treatment analysis of patients after EVAR was performed in 171 patients. Aneurysm neck morphology was quantified using the aneurysm severity grading (ASG) neck score calculated on preoperative computed tomography angiography images. The ASG neck score was used to predict proximal endograft failure. Receiver operating characteristic analysis was performed to calculate a threshold to divide favorable and unfavorable aneurysm necks (low and high risk); positive and negative likelihood-ratios were calculated accordingly. Freedom from proximal endograft failure was compared between groups using Kaplan-Meier analysis. RESULTS: During a median follow-up of 7.6 years, 20 patients suffered proximal endograft failure. Receiver operating characteristic analysis showed an area under the curve of 0.77 (95% confidence interval [CI], 0.65-0.90; P < .001), indicating acceptable prediction. The threshold was determined at ASG neck score ≥5; 30 patients had unfavorable neck morphology, of whom 11 developed proximal endograft failure. The positive likelihood-ratio was 4.4 (95% CI, 2.5-7.8), and the negative likelihood-ratio was 0.51 (95% CI, 0.3-0.8). Twelve years postoperatively, freedom from proximal endograft failure was 91.7% in the favorable group and 53.2% in the unfavorable group, a difference of 38.5% (95% CI, 13.9-63.1; P < .001). CONCLUSIONS: In this study, the ASG neck score predicted proximal endograft failure during the entire follow-up. This exhibits the persistent risk for proximal endograft failure long after EVAR and calls for ongoing surveillance especially in patients with unfavorable aneurysm necks.

Systematic review of embolization of type I endoleaks using liquid embolic agents.

OBJECTIVE: The long-term success of endovascular aneurysm repair (EVAR) is limited by complications, most importantly endoleaks. In case of (persistent) type I endoleak (T1EL), secondary intervention is indicated to prevent secondary aneurysm rupture. Different treatment options are suggested for T1ELs, such as endo anchors, (fenestrated) cuffs, embolization, or open conversion. Currently, the treatment of T1EL with liquid embolic agents is available; however, results are not yet addressed. This review presents the safety and efficacy of embolization with liquid embolic agents for treatment of T1ELs after EVAR. METHODS: A systematic literature search was performed for all studies reporting the use of liquid embolic agents as monotherapy for treatment of T1ELs after EVAR. Patient numbers, technical success (successful delivery of liquid embolics in the T1EL) and clinical success (absence of aneurysm related death, endoleak recurrence or additional interventions during follow-up) were examined. RESULTS: Of 1604 articles, 10 studies met the selection criteria, including 194 patients treated with liquid embolics; 73.2% of the patients were male with a median age of 71 years. The overall technical success was 97.9%. Clinical success was 87.6%. Because the median follow-up was only 13.0 months (range, 1-89 months), data on long-term success are almost absent. Four cases (2.1%) of secondary aneurysm rupture after embolization owing to endoleak recurrence were reported. All ruptures occurred in aneurysms exceeding initial treatment diameter of 70 mm. CONCLUSIONS: Initial technical success after liquid embolization for T1EL is high, although long-term clinical success rates are lacking. Within this review, the risk of secondary rupture is comparable with untreated T1EL at 2% with a median follow-up of 13 months, regardless of the initial success of embolization. In general, no decrease in secondary aneurysm rupture after embolization of T1EL after EVAR is demonstrated, although the results of late embolization are debated.

Inflammatory Gene Expression of Human Perivascular Adipose Tissue in Abdominal Aortic Aneurysms.

OBJECTIVE: Perivascular adipose tissue (PVAT) contributes to vascular homeostasis and is increasingly linked to vascular pathology. PVAT density and volume were associated with abdominal aortic aneurysm (AAA) presence and dimensions on imaging. However, mechanisms underlying the role of PVAT in AAA have not been clarified. This study aimed to explore differences in PVAT from AAA using gene expression and functional tests. METHODS: Human aortic PVAT and control subcutaneous adipose tissue were collected during open AAA surgery. Gene analyses and functional tests were performed. The control group consisted of healthy aorta from non-living renal transplant donors. Gene expression tests were performed to study genes potentially involved in various inflammatory processes and AAA related genes. Live PVAT and subcutaneous adipose tissue (SAT) from AAA were used for ex vivo co-culture with smooth muscle cells (SMCs) retrieved from non-pathological aortas. RESULTS: Adipose tissue was harvested from 27 AAA patients (n [gene expression] = 22, n [functional tests] = 5) and five control patients. An increased inflammatory gene expression of PTPRC (p = .008), CXCL8 (p = .033), LCK (p = .003), CCL5 (p = .004) and an increase in extracellular matrix breakdown marker MMP9 (p = .016) were found in AAA compared with controls. Also, there was a decreased anti-inflammatory gene expression of PPARG in AAA compared with controls (p = .040). SMC co-cultures from non-pathological aortas with PVAT from AAA showed increased MMP9 (p = .033) and SMTN (p = .008) expression and SAT increased SMTN expression in these SMC. CONCLUSION: The data revealed that PVAT from AAA shows an increased pro-inflammatory and matrix metallopeptidase gene expression and decreased anti-inflammatory gene expression. Furthermore, increased expression of genes involved in aneurysm formation was found in healthy SMC co-culture with PVAT of AAA patients. Therefore, PVAT from AAA might contribute to inflammation of the adjacent aortic wall and thereby plays a possible role in AAA pathophysiology. These proposed pathways of inflammatory induction could reveal new therapeutic targets in AAA treatment.

Patient-Specific 3-Dimensional Model of Smooth Muscle Cell and Extracellular Matrix Dysfunction for the Study of Aortic Aneurysms.

INTRODUCTION: Abdominal aortic aneurysms (AAAs) are associated with overall high mortality in case of rupture. Since the pathophysiology is unclear, no adequate pharmacological therapy exists. Smooth muscle cells (SMCs) dysfunction and extracellular matrix (ECM) degradation have been proposed as underlying causes. We investigated SMC spatial organization and SMC-ECM interactions in our novel 3-dimensional (3D) vascular model. We validated our model for future use by comparing it to existing 2-dimensional (2D) cell culture. Our model can be used for translational studies of SMC and their role in AAA pathophysiology. MATERIALS AND METHODS: SMC isolated from the medial layer of were the aortic wall of controls and AAA patients seeded on electrospun poly-lactide-co-glycolide scaffolds and cultured for 5 weeks, after which endothelial cells (EC) are added. Cell morphology, orientation, mechanical properties and ECM production were quantified for validation and comparison between controls and patients. RESULTS: We show that cultured SMC proliferate into multiple layers after 5 weeks in culture and produce ECM proteins, mimicking their behavior in the medial aortic layer. EC attach to multilayered SMC, mimicking layer interactions. The novel SMC model exhibits viscoelastic properties comparable to biological vessels; cytoskeletal organization increases during the 5 weeks in culture; increased cytoskeletal alignment and decreased ECM production indicate different organization of AAA patients' cells compared with control. CONCLUSION: We present a valuable preclinical model of AAA constructed with patient specific cells with applications in both translational research and therapeutic developments. We observed SMC spatial reorganization in a time course of 5 weeks in our robust, patient-specific model of SMC-EC organization and ECM production.

One-Year Single-Center Results of the Multilayer Flow Modulator Stents for the Treatment of Type B Aortic Dissection.

PURPOSE: To report a single-center series of patients with type B aortic dissection treated with the Multilayer Flow Modulator (MFM). MATERIALS AND METHODS: Over a 36-month period, 23 patients (median age 53 years; 20 men) with complicated type B aortic dissections (2 acute, 5 subacute, and 16 chronic) were treated with the MFM. Primary endpoints of rupture or dissection-related death, overall mortality, and reintervention were evaluated using the Kaplan-Meier method; estimates for freedom from the endpoints are reported with the 95% confidence interval (CI). Secondary outcomes included technical success, adverse events, and aortic remodeling. Clinical and imaging data were collected preoperatively, directly postoperatively, and annually to 36 months for analysis using computational fluid dynamics (CFD). RESULTS: Initial technical success was 91.3%. The estimates of the endpoints at 12 months were 100% for freedom from rupture or aortic-related death, 95.7% for freedom from overall mortality, and 91.3% for freedom from reintervention. No device-related neurological or systemic complications occurred, and no additional reinterventions were needed during follow-up. A total of 144 branches overstented by the MFM remained patent. Morphologic analysis of the aortic dissection showed progressive true lumen volume increase (75.9%, p<0.001) with concomitant false lumen volume decrease (42.8%, p<0.001); the CFD analyses showed increased laminar flow. CONCLUSION: In the current series, the MFM provided a safe and feasible treatment option for complicated acute, subacute, and chronic type B aortic dissections, with high technical success, low mortality, and active aortic remodeling. Further studies should elucidate the long-term safety of the MFM and its effectiveness in a larger patient cohort.

Small bowel obstruction caused by 18FDG-negative ileocecal metastasis of lobular breast carcinoma.

Breast carcinoma is the most frequently diagnosed cancer in women. In up to 30%, distant metastases will occur; however, ileocecal metastases are rare. Although there have been cases reported that demonstrate ileocecal metastases of breast carcinoma, PET/CT-negative cases have never been described. We present a patient with a small bowel obstruction, preoperatively complicated by pulmonary embolisms. The patient underwent placement of an inferior vena cava filter followed by hemicolectomy. Pathological examination revealed ileocecal lobular breast carcinoma metastases and adjacent peritoneal carcinomatosis, which had shown no intestinal 18FDG uptake 7 weeks prior to presentation. Subsequently, symptoms of metastases and the paraneoplastic syndrome progressed, and the patient was referred to the medical oncologist for palliative therapy. Although uncommon, physicians should be aware of potential presence of 18FDG-negative gastrointestinal metastases of breast cancer.

Geometric Analysis of Type B Aortic Dissections Shows Aortic Remodeling After Intervention Using Multilayer Stents.

Recently, multilayer stents for type B aortic dissections (TBAD) have been proposed to decrease false lumen flow, increase and streamline true lumen flow, and retain branch vessel patency. We aimed to provide a protocol with standardized techniques to investigate aortic remodeling of TBAD by multilayer flow modulators (MFM) in static geometric and hemodynamic analyses. Combining existing literature and new insights, a standardized protocol was designed. Using pre- and postoperative CT scans, geometric models were constructed, lumen dimensions were calculated, computational fluid dynamics (CFD) models were composed, and velocity and pressures were calculated. Sixteen TBAD cases treated with MFM were included for analysis. For each case, aortic remodeling was analyzed using post-processing medical imaging software. After 3D models were created, geometrical anatomical measurements were performed, and meshes for finite element analysis were generated. MFM cases were compared pre- and postoperatively; true lumen volumes increased (p < 0.001), false lumen volumes decreased (p = 0.001), true lumen diameter at the plane of maximum compression (PMC) increased (p < 0.001), and false lumen index decreased (p = 0.008). True lumen flow was streamlined, and the overall fluid velocity and pressures decreased (p < 0.001 and p = 0.006, respectively). This protocol provided a standardized method to evaluate the effects of MFM treatments in TBAD on geometric analyses, PMC, and CFD outcomes.

Gutter Characteristics and Stent Compression of Self-Expanding vs Balloon-Expandable Chimney Grafts in Juxtarenal Aneurysm Models.

Purpose: To assess in silicone juxtarenal aneurysm models the gutter characteristics and compression of different types of chimney graft (CG) configurations. Materials and Methods: Fifty-seven combinations of Excluder C3 or Conformable Excluder stent-grafts (23, 26, and 28.5 mm) were deployed in 2 silicone juxtarenal aneurysm models with 3 types of CGs: Viabahn self-expanding (VSE; 6 and 13 mm) or Viabahn balloon-expandable (VBX; 6, 10, and 12 mm) stent-grafts and Advanta V12 balloon-expandable stent-grafts (ABX; 6 and 12 mm). Setups were divided into 4 groups on the basis of increasing CG and main graft (MG) diameters. Two independent observers assessed gutter size and type as well as CG compression on computed tomography scans using postprocessing software. Results: In the smaller diameter combinations (6-mm CG and 23-, 26-, and 28.5-mm MGs), both VSE (p=0.006 to 0.050) and ABX (p=0.045 to 0.050) showed lower gutter areas and volumes compared with VBX. In turn, the VBX showed a nonsignificant tendency to decreased compression, especially compared to ABX. Use of the Excluder C3 showed a 6-fold increase in type A1 gutters (related to type Ia endoleak) as compared to the Conformable Excluder (p=0.018). Balloon-expandable stent-grafts (both ABX and VBX) showed a 3-fold increase in type A1 gutters in comparison with self-expanding stent-grafts (p=0.008). Conclusion: The current study suggests that use of the Conformable Excluder in combination with VSE chimney grafts is superior to the other tested CG/MG combinations in terms of gutter size, gutter type, and CG compression.

A multilayer micromechanical elastic modulus measuring method in ex vivo human aneurysmal abdominal aortas.

Abdominal aortic aneurysms (AAA) are common and potentially life-threatening aortic dilatations, due to the effect of hemodynamic changes on the aortic wall. Previous research has shown a potential pathophysiological role for increased macroscopic aneurysmal wall stiffness; however, not investigating micromechanical stiffness. We aimed to compile a new protocol to examine micromechanical live aortic stiffness (elastic moduli), correlated to histological findings with quantitative immunofluorescence (QIF). Live AAA biopsies (n = 7) and non-dilated aortas (controls; n = 3) were sectioned. Local elastic moduli of aortic intima, media and adventitia were analysed in the direction towards the lumen and vice versa with nanoindentation. Smooth muscle cells (SMC), collagen and fibroblasts were examined using QIF. Nanoindentation of AAA vs. controls demonstrated a 4-fold decrease in elastic moduli (p = 0.022) for layers combined and a 26-fold decrease (p = 0.017) for media-to-intima direction. QIF of AAA vs. controls revealed a 4-, 3- and 6-fold decrease of SMC, collagen and fibroblasts, respectively (p = 0.036). Correlations were found between bidirectional intima and media measurements (ρ = 0.661, p = 0.038) and all QIF analyses (ρ = 0.857-0.905, p = 0.002-0.007). We present a novel protocol to analyse microscopic elastic moduli in live aortic tissues using nanoindentation. Hence, our preliminary findings of decreased elastic moduli and altered wall composition warrant further microscopic stiffness investigation to potentially clarify AAA pathophysiology and to explore potential treatment by wall strengthening. STATEMENT OF SIGNIFICANCE: Although extensive research on the pathophysiology of dilated abdominal aortas (aneurysms) has been performed, the exact underlying pathways are still largely unclear. Previously, the macroscopic stiffness of the pathologic and healthy aortic wall has been studied. This study however, for the first time, studied the microscopic stiffness changes in live tissue of dilated and non-dilated abdominal aortas. This new protocol provides a device to analyse the alterations on cellular level within their microenvironment, whereas previous studies studied the aorta as a whole. Outcomes of these measurements might help to better understand the underlying origin of the incidence and progression of aneurysms and other aortic diseases.

Impaired smooth muscle cell contractility as a novel concept of abdominal aortic aneurysm pathophysiology.

Ruptured abdominal aortic aneurysms (AAA) are associated with overall mortality rates up to 90%. Despite extensive research, mechanisms leading to AAA formation and advancement are still poorly understood. Smooth muscle cells (SMC) are predominant in the aortic medial layer and maintain the wall structure. Apoptosis of SMC is a well-known phenomenon in the pathophysiology of AAA. However, remaining SMC function is less extensively studied. The aim of this study is to assess the in vitro contractility of human AAA and non-pathologic aortic SMC. Biopsies were perioperatively harvested from AAA patients (n = 21) and controls (n = 6) and clinical data were collected. Contractility was measured using Electric Cell-substrate Impedance Sensing (ECIS) upon ionomycin stimulation. Additionally, SMC of 23% (5 out of 21) of AAA patients showed impaired maximum contraction compared to controls. Also, SMC from patients who underwent open repair after earlier endovascular repair and SMC from current smokers showed decreased maximum contraction vs. controls (p = 0.050 and p = 0.030, respectively). Our application of ECIS can be used to study contractility in other vascular diseases. Finally, our study provides with first proof that impaired SMC contractility might play a role in AAA pathophysiology.

Repeat Rupture of a Giant Abdominal Aortic Aneurysm after EVAR.

INTRODUCTION: Ruptured abdominal aortic aneurysms (AAAs) are known to be associated with high fatal outcomes. Giant AAAs are often defined as having a maximum diameter over 13 cm. Large AAAs over 8 cm have demonstrated a yearly rupture rate of 30-50%, which explains the rarity of giant AAAs. Endovascular repair of ruptured AAAs (rAAAs) is increasingly advocated because of the shorter hospital stay and fewer post-operative complications. Nonetheless, outcomes regarding mortality and cost-effectiveness show a large variability and long-term outcomes are lacking. Few data have been published on treatment of giant AAAs and rAAAs; however, open surgery is generally the preferred option. REPORT: An 83 year old presented to the Emergency Department with a history of ruptured abdominal aortic aneurysm treated with an aorto-uni-iliac endograft and a femorofemoral crossover bypass. During follow up, this was complicated by a symptomatic type III endoleak, which was treated by endovascular repair. During the current admission, he presented with a re-rupture of his former aneurysm, which now was 18 cm diameter because of a type IA endoleak. Open surgical repair was performed and the post-operative course was without complications. DISCUSSION: The current case underlines the value of vascular surgeons being able to perform both open and endovascular surgery in rAAA.

Secondary Fill Minimizes Gutter Size in Chimney EVAS Configurations In Vitro.

PURPOSE: To investigate in an in vitro model if secondary endobag filling can reduce gutter size during chimney endovascular aneurysm sealing (chEVAS). MATERIALS AND METHODS: Nellix EVAS systems were deployed in 2 silicone juxtarenal aneurysm models with suprarenal aortic diameters of 19 and 24 mm. Four configurations were tested: EVAS with 6-mm balloon-expandable (BE) or self-expanding (SE) chimney grafts (CGs) in the renal branches of both models. Balloons were inflated simultaneously in the CGs and main endografts during primary and secondary endobag filling and polymer curing. Computed tomography (CT) was performed immediately after the primary and secondary fills. Cross-sectional lumen areas were measured on the CT images to calculate gutter volumes and percent change. CG compression was calculated as the reduction in lumen surface area measured perpendicular to the central lumen line. The largest gutter volume and highest compression were presented per CG configuration per model. RESULTS: Secondary endobag filling reduced the largest gutter volumes from 99.4 to 73.1 mm3 (13.2% change) and 84.2 to 72.0 mm3 (27.6% change) in the BECG configurations and from 67.2 to 44.0 mm3 (34.5% change) and 92.7 to 82.3 mm3 (11.2% change) in the SECG configurations in the 19- and 24-mm models, respectively. Secondary endobag filling increased CG compression in 6 of 8 configurations. BECG compression changed by -0.2% and 5.4% and by -1.0% and 0.4% in the 19- and 24-mm models, respectively. SECG compression changed by 10.2% and 16.0% and by 7.2% and 7.3% in the 19- and 24-mm models, respectively. CONCLUSION: Secondary endobag filling reduced paragraft gutters; however, this technique did not obliterate them. Increased CG compression and prolonged renal ischemia time should be considered if secondary endobag filling is used.

High Density of Periaortic Adipose Tissue in Abdominal Aortic Aneurysm.

OBJECTIVES: Perivascular adipose tissue (PVAT) is currently seen as a paracrine organ that produces vasoactive substances, including inflammatory agents, which may have an impact on the vasculature. In this study PVAT density was quantified in patients with an aortic aneurysm and compared with those with a non-dilated aorta. Since chronic inflammation, as the pathway to medial thinning, is a hallmark of abdominal aortic aneurysms (AAAs), it was hypothesised that PVAT density is higher in AAA patients. METHODS: In this multicentre retrospective case control study, three groups of patients were included: non-treated asymptomatic AAA (n = 140), aortoiliac occlusive disease (AIOD) (n = 104), and individuals without aortic pathology (n = 97). A Hounsfield units based analysis was performed by computed tomography (CT). As a proxy for PVAT, the density of adipose tissue 10 mm circumferential to the infrarenal aorta was analysed in each consecutive CT slice. Intra-individual PVAT differences were reported as the difference in PVAT density between the region of the maximum AAA diameter (or the mid-aortic region in patients with AIOD or controls) and the two uppermost slices of infrarenal non-dilated aorta just below the renal arteries. Furthermore, subcutaneous (SAT) and visceral (VAT) adipose tissue measurements were performed. Linear models were fitted to assess the association between the study groups, different adipose tissue compartments, and between adipose tissue compartments and aortic dimensions. RESULTS: AAA patients presented higher intra-individual PVAT differences, with higher PVAT density around the aneurysm sac than the healthy neck. This association persisted after adjustment for cardiovascular risk factors and diseases and other fat compartments (ß = 13.175, SE 4.732, p = .006). Furthermore, intra-individual PVAT differences presented the highest correlation with aortic volume that persisted after adjustment for other fat compartments, body mass index, sex, and age (ß = 0.566, 0.200, p = .005). CONCLUSION: The results suggest a relation between the deposition of PVAT and AAA pathophysiology. Further research should explore the exact underlying processes.

Systematic Review of Circulating, Biomechanical, and Genetic Markers for the Prediction of Abdominal Aortic Aneurysm Growth and Rupture.

BACKGROUND: The natural course of abdominal aortic aneurysms (AAA) is growth and rupture if left untreated. Numerous markers have been investigated; however, none are broadly acknowledged. Our aim was to identify potential prognostic markers for AAA growth and rupture. METHODS AND RESULTS: Potential circulating, biomechanical, and genetic markers were studied. A comprehensive search was conducted in PubMed, Embase, and Cochrane Library in February 2017, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Study selection, data extraction, and methodological quality assessment were conducted by 2 independent researchers. Plausibility of markers was based on the amount of publications regarding the marker (more than 3), pooled sample size (more than 100), bias risk and statistical significance of the studies. Eighty-two studies were included, which examined circulating (n=40), biomechanical (n=27), and genetic markers (n=7) and combinations of markers (n=8). Factors with an increased expansion risk included: AAA diameter (9 studies; n=1938; low bias risk), chlamydophila pneumonia (4 studies; n=311; medium bias risk), S-elastin peptides (3 studies; n=205; medium bias risk), fluorodeoxyglucose uptake (3 studies; n=104; medium bias risk), and intraluminal thrombus size (5 studies; n=758; medium bias risk). Factors with an increased rupture risk rupture included: peak wall stress (9 studies; n=579; medium bias risk) and AAA diameter (8 studies; n=354; medium bias risk). No meta-analysis was conducted because of clinical and methodological heterogeneity. CONCLUSIONS: We identified 5 potential markers with a prognostic value for AAA growth and 2 for rupture. While interpreting these data, one must realize that conclusions are based on small sample sizes and clinical and methodological heterogeneity. Prospective and methodological consonant studies are strongly urged to further study these potential markers.

An in vitro method to keep human aortic tissue sections functionally and structurally intact.

The pathophysiology of aortic aneurysms (AA) is far from being understood. One reason for this lack of understanding is basic research being constrained to fixated cells or isolated cell cultures, by which cell-to-cell and cell-to-matrix communications are missed. We present a new, in vitro method for extended preservation of aortic wall sections to study pathophysiological processes. Intraoperatively harvested, live aortic specimens were cut into 150 µm sections and cultured. Viability was quantified up to 92 days using immunofluorescence. Cell types were characterized using immunostaining. After 14 days, individual cells of enzymatically digested tissues were examined for cell type and viability. Analysis of AA sections (N = 8) showed a viability of 40% at 7 days and smooth muscle cells, leukocytes, and macrophages were observed. Protocol optimization (N = 4) showed higher stable viability at day 62 and proliferation of new cells at day 92. Digested tissues showed different cell types and a viability up to 75% at day 14. Aortic tissue viability can be preserved until at least 62 days after harvesting. Cultured tissues can be digested into viable single cells for additional techniques. Present protocol provides an appropriate ex vivo setting to discover and study pathways and mechanisms in cultured human aneurysmal aortic tissue.