Atherosclerotic Abdominal Aortic Aneurysm Research Articles

The contribution of matrix metalloproteinases and their inhibitors to the development, progression, and rupture of abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAAs) account for up to 8% of deaths in men aged 65 years and over and 2.2% of women. Patients with AAAs often have atherosclerosis, and intimal atherosclerosis is generally present in AAAs. Accordingly, AAAs are considered a form of atherosclerosis and are frequently referred to as atherosclerotic aneurysms. Pathological observations advocate inflammatory cell infiltration alongside adverse extracellular matrix degradation as key contributing factors to the formation of human atherosclerotic AAAs. Therefore, macrophage production of proteolytic enzymes is deemed responsible for the damaging loss of ECM proteins, especially elastin and fibrillar collagens, which characterise AAA progression and rupture. Matrix metalloproteinases (MMPs) and their regulation by tissue inhibitors metalloproteinases (TIMPs) can orchestrate not only ECM remodelling, but also moderate the proliferation, migration, and apoptosis of resident aortic cells, alongside the recruitment and subsequent behaviour of inflammatory cells. Accordingly, MMPs are thought to play a central regulatory role in the development, progression, and eventual rupture of abdominal aortic aneurysms (AAAs). Together, clinical and animal studies have shed light on the complex and often diverse effects MMPs and TIMPs impart during the development of AAAs. This dichotomy is underlined from evidence utilising broad-spectrum MMP inhibition in animal models and clinical trials which have failed to provide consistent protection from AAA progression, although more encouraging results have been observed through deployment of selective inhibitors. This review provides a summary of the supporting evidence connecting the contribution of individual MMPs to AAA development, progression, and eventual rupture. Topics discussed include structural, functional, and cell-specific diversity of MMP members; evidence from animal models of AAA and comparisons with findings in humans; the dual role of MMPs and the requirement to selectively target individual MMPs; and the advances in identifying aberrant MMP activity. As evidenced, our developing understanding of the multifaceted roles individual MMPs perform during the progression and rupture of AAAs, should motivate clinical trials assessing the therapeutic potential of selective MMP inhibitors, which could restrict AAA-related morbidity and mortality worldwide.

Differences in local immune cell landscape between Q fever and atherosclerotic abdominal aortic aneurysms identified by multiplex immunohistochemistry.

Chronic Q fever is a zoonosis caused by the bacterium Coxiella burnetii which can manifest as infection of an abdominal aortic aneurysm (AAA). Antibiotic therapy often fails, resulting in severe morbidity and high mortality. Whereas previous studies have focused on inflammatory processes in blood, the aim of this study was to investigate local inflammation in aortic tissue. Multiplex immunohistochemistry was used to investigate local inflammation in Q fever AAAs compared to atherosclerotic AAAs in aorta tissue specimen. Two six-plex panels were used to study both the innate and adaptive immune systems. Q fever AAAs and atherosclerotic AAAs contained similar numbers of CD68+ macrophages and CD3+ T cells. However, in Q fever AAAs, the number of CD68+CD206+ M2 macrophages was increased, while expression of GM-CSF was decreased compared to atherosclerotic AAAs. Furthermore, Q fever AAAs showed an increase in both the number of CD8+ cytotoxic T cells and CD3+CD8-FoxP3+ regulatory T cells. Finally, Q fever AAAs did not contain any well-defined granulomas. These findings demonstrate that despite the presence of pro-inflammatory effector cells, persistent local infection with C. burnetii is associated with an immune-suppressed microenvironment. This work was supported by SCAN consortium: European Research Area - CardioVascualar Diseases (ERA-CVD) grant [JTC2017-044] and TTW-NWO open technology grant [STW-14716].

Discovery of potential biomarkers for human atherosclerotic abdominal aortic aneurysm through untargeted metabolomics and transcriptomics.

Abdominal aortic aneurysm (AAA) and atherosclerosis (AS) have considerable similarities in clinical risk factors and molecular pathogenesis. The aim of our study was to investigate the differences between AAA and AS from the perspective of metabolomics, and to explore the potential mechanisms of differential metabolites via integration analysis with transcriptomics. Plasma samples from 32 AAA and 32 AS patients were applied to characterize the metabolite profiles using untargeted liquid chromatography-mass spectrometry (LC-MS). A total of 18 remarkably different metabolites were identified, and a combination of seven metabolites could potentially serve as a biomarker to distinguish AAA and AS, with an area under the curve (AUC) of 0.93. Subsequently, we analyzed both the metabolomics and transcriptomics data and found that seven metabolites, especially 2'-deoxy-D-ribose (2dDR), were significantly correlated with differentially expressed genes. In conclusion, our study presents a comprehensive landscape of plasma metabolites in AAA and AS patients, and provides a research direction for pathogenetic mechanisms in atherosclerotic AAA.

Galectin-1 prevents pathological vascular remodeling in atherosclerosis and abdominal aortic aneurysm

Background and Aims: Aim: Pathological vascular remodeling is the underlying cause of main cardiovascular diseases (CVD) including atherosclerosis and abdominal aortic aneurysm (AAA). Diminished vascular smooth muscle cell (VSMC) content is a key mechanism of atherosclerotic plaques and AAA instability. We hypothesized that Galectin-1 (Gal-1) could exert protective effects in atherosclerosis and AAA as previously demonstrated in different chronic and acute inflammatory diseases.

Inhibition of CXCR2 alleviates the development of abdominal aortic aneurysm in Apo E-/- mice.

ABSTRACTPurposeTo investigate the relationship between atherosclerotic abdominal aortic aneurysm (AAA) and CXC chemokine receptor type 2 (CXCR2).MethodsMouse AAA model was established by embedding angiotensin-II pump (1000 ng/kg/min) in ApoE-/- mice. Mice were received SB225002, a selective CXCR2 antagonist, for treatment. Blood pressure was recorded, and CXCR2+ macrophages were examined by flow cytometry analysis. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining was performed to detect cell apoptosis of abdominal aortic aneurysms. Macrophages were isolated from ApoE-/- mice and treated with Ang II and/or SB225002. Dihydroethidium staining was carried out to determine reactive oxygen species (ROS) activity. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the production of IL-1β and TNF-α. The corresponding gene expressions were measured using real-time polymerase chain reaction (PCR), western blot, and immunohistochemistry staining.ResultsWe found that Ang II activated the expression of CXCR2 in monocytes during the formation of AAA. Inhibition of CXCR2 significantly reduced the size of AAA, attenuated inflammation and phenotypic changes in blood vessels. Ang II-induced macrophages exhibited elevated ROS activity, and elevated levels of 1β and TNF-α, which were then partly abolished by SB225002.ConclusionsCXCR2 plays an important role in AAA, suggesting that inhibiting CXCR2 may be a new treatment for AAA.

Microcalcification: A pathological characteristic and mediator of abdominal aortic aneurysm formation

Background and Aims: Abdominal aortic aneurysms (AAAs) are highly lethal diseases without effective clinical predictors and therapeutic targets. Vascular microcalcification as detected by fluorine-18-sodium fluoride (18F-NaF) has recently been recognized as a valuable indicator in predicting of atherosclerotic plaque rupture and AAA expansion. However, whether vascular microcalcification is involved in the pathogenesis of AAA remains elusive.

Runx2 (Runt-Related Transcription Factor 2)-Mediated Microcalcification Is a Novel Pathological Characteristic and Potential Mediator of Abdominal Aortic Aneurysm

Abdominal aortic aneurysms (AAAs) are highly lethal diseases without effective clinical predictors and therapeutic targets. Vascular microcalcification, as detected by fluorine-18-sodium fluoride, has recently been recognized as a valuable indicator in predicting atherosclerotic plaque rupture and AAA expansion. However, whether vascular microcalcification involved in the pathogenesis of AAA remains elusive. Approach and Results: Microcalcification was analyzed in human aneurysmal aortas histologically and in AngII (angiotensin II)-infused ApoE-/- mouse aortas by fluorine-18-sodium fluoride positron emission tomography and X-ray computed tomography scanning in chronological order in live animals. AAA patients' aortic tissue showed markedly enhanced microcalcification in the aortic media within the area proximal to elastic fiber degradation, compared with non-AAA patients. Enhanced fluorine-18-sodium fluoride uptake preceded significant aortic expansion in mice. Microcalcification-positive mice on day 7 of AngII infusion showed dramatic aortic expansion on subsequent days 14 to 28, whereas microcalcification-negative AngII-infused mice and saline-induced mice did not develop AAA. The application of hydroxyapatite, the main component of microcalcification, aggravated AngII-induced AAA formation in vivo. RNA-sequencing analysis of the suprarenal aortas of 4-day-AngII-infused ApoE-/- mice and bioinformatics analysis with ChIP-Atlas database identified the potential involvement of the osteogenic transcriptional factor Runx2 (runt-related transcription factor 2) in AAA. Consistently, vascular smooth muscle cell-specific Runx2 deficiency markedly repressed AngII-induced AAA formation in the ApoE-/- mice compared with the control littermates. Our studies have revealed microcalcification as a novel pathological characteristic and potential mediator of AAA, and targeting microcalcification may represent a promising strategy for AAA prevention and treatment.

ASPECTS OF SURGICAL TREATMENT OF GIANT ATHEROSCLEROTIC ABDOMINAL AORTIC ANEURYSMS

The article deals with some aspects of surgical treatment of giant atherosclerotic abdominal aortic aneurysms. Giant aneurysms measuring more than 10 cm in diameter are an extremely rare disorder. A total of 33 observations of surgical treatment of patients with this disorder are described in the English language literature. This article provides epidemiology data based on the publications we studied. Clinical cases described in both domestic and foreign literature are presented and reviewed. A summary table has been created on the basis of the data, which provides comprehensive information on the experience accumulated over the given time in the treatment of gigantic aortic aneurysms. Over 600 surgeries for abdominal aortic aneurysms, of which nine interventions for gigantic aneurysms, have been performed in A.V.Vishnevsky National Medical Research Institute of Surgery. So far, this is the largest experience in surgery of gigantic aortic aneurysms accumulated in one institution. The article presents an analysis of literature data in the context of the results of our own observations. The aspects of choosing the surgical treatment method, the advantages and disadvantages of both open interventions and endovascular operations were considered in detail. The authors described in detail the features of the choice of surgical access, the technique for isolating the aneurysm neck with a detailed analysis of the further course of the operation. Extensive visual material is presented such as CT-, CT angiography scans, intraoperative photographs. The outcomes of interventions are analysed, the mortality rate of post-surgical treatment of giant aneurysms is 0%, there is no significant difference in morbidity in comparison with surgery of smaller aneurysms.

Inflammatory abdominal aortic aneurysms: place of Ig G4related diseases

Aim. Inflammatory abdominal aortic aneurysm may be one of the manifestations of Ig G4-related disease. This study analyzes the clinical manifestations of Ig G4related inflammatory abdominal aortic aneurysm. Material and methods. We examined twenty patients with abdominal aortic aneurysm (AAA). The clinical performance of the disease, the results of laboratory and pathomorphological studies were studied. In 8 cases, Ig G4-related inflammatory AAA criteria were identified. Results. Compared to atherosclerotic AAA, Ig G4-related cases were characterized by a less frequent presence of abdomen or back pain. The concentration of IgG4 in serum in Ig G4-related cases was significantly increased. Patients with Ig G4-related inflammatory AAA often had a history of allergic reactions to drugs, autoimmune diseases, a high concentration of Ig E and a high titer of antinuclear antibodies in blood serum. According to a histological study of intraoperative biopsy samples, Ig G4-related cases were characterized by thickening of adventitia and numerous infiltrates with Ig G4-positive plasma cells. Conclusion. The presence of Ig G4-related disease is diagnosed in the presence of irregular fibrous tissue proliferation with Ig G4 plasma cell infiltrates and with an increase in the concentration of Ig G4 in blood serum. Ig G4-related inflammatory AAA has clinical specifics in comparison with atherosclerotic aneurysm.

TECHNIQUE FOR RESECTION OF ATHEROSCLEROTIC ABDOMINAL AORTIC ANEURYSM WITH ANOMALOUS ORIGIN OF RENAL ARTERIES AND PELVIC DYSTOPIA OF THE LEFT KIDNEY

This article describes the clinical observation of a patient with an atherosclerotic abdominal aortic aneurysm and pelvic dystopia of the left kidney. Due to the anomalous origin of renal arteries, we have chosen a method of treatment consisted of resection and an aortic prosthetics and reimplantation of vessels extending from the aortic aneurysm. 5 years after surgery, the patient had an aneurysm of the left iliac artery, which required repeated intervention. Our approach allowed us to preserve all the renal arteries and renal function.

A METHOD OF RESECTION AND REPLACEMENT OF THE ABDOMINAL AORTA IN PATIENTS WITH INFRARENAL ABDOMINAL AORTIC ANEURYSMS AND SEVERE COMORBID CORONARY PATHOLOGY

This article presents a clinical observation of a patient with a giant atherosclerotic abdominal aortic aneurysm and comorbid uncorrected coronary artery disease. Taking into account the threat of aneurysm rupture, we have chosena surgical intervention using methods that reduce the risk of cardiovascular events in the perioperative period: the distal-first technique allowed us to reduce the aortic clamping time, and the use of temporary axillofemoral bypass grafting reduced peripheral resistance and stress on myocardium.

Investigation of an Immunogenetic Profile in Patients with Abdominal Aortic Aneurysms and Possible Applications in Screening and Surveillance

The pathogenesis of atherosclerotic abdominal aortic aneurysms (AAAs) remains not fully understood. Histological analyses confirm chronic adventitial and medial inflammatory cell infiltration, and its pathophysiology involves the upregulation of proteolytic pathways; added to this, genetic factors have been suggested to favor the susceptibility for AAA. The aim of the present study was to analyze the association between genetic polymorphism of the class II human leukocyte antigens (HLAs, HLA-DRB1) with the susceptibility to develop AAA in Mexican patients and to initiate a pilot study of single-nucleotide polymorphisms (SNPs) rs1024611 in the monocyte chemoattractant protein-1 (MCP-1/CCL2) gene to investigate a possible role in the AAA pathogenesis. In a cohort of patients with AAA, HLA molecular typing was completed for DRB1 loci with LABType SSO-One Lambda kit in 39 patients (69% men with a mean age of 72years) and compared with 99 without the disease (60% men, mean age 65years) (control group). Genotyping of rs1024611 in the MCP-1 gene was performed using TaqMan predesigned SNP genotyping assays in 27 patients with AAA (63% men, mean age of 71). Gene frequencies (gfs) and genotype frequencies (Gfs) were determined; categorical data were analyzed by nonparametric statistic test at significance level (P<0.05), and odds ratios (ORs) were calculated using the STATA v14 software and StatCalc software Epi Info™ 7.2.2.2. Seventy-eight HLA-DRB1 alleles of patients with AAA and 198 from the control group were studied. We observed that the gf of HLA-DRB1*01 was 0.128 in the AAA group compared with 0.05 in the control group (P=0.03, OR: 2.6, 95% confidence interval [CI]: 1.04-6.5); the gf of HLA-DRB1*16 was 0.115 in the AAA and 0.025 in control group (P=0.002, OR: 5, 95% CI: 1.6-16.9). The Gf for SNP rs1024611 were 0.51 in the GA genotype, 0.30 in AA, and 0.19 of GG. Four patients with the proinflammatory homozygous genotype GG (80%) were women and younger than patients with other genotypes, and only one had a history of dyslipidemia. The dissection and interpretation of an immunogenetic profile in patients with AAA is an active and complex field of research that might assist in a more precise identification of those patients at genetic risk. Our study demonstrated increased frequencies of HLA-DRB1*01 and HLA-DRB1*16 alleles in Mexican patients with AAA compared with an ethnically matched control group.

Acute non-traumatic disease of the abdominal aorta.

Acute pathology in the abdominal aorta is associated with significant morbidity and mortality. The most feared complication of abdominal aortic disease is acute rupture in the setting of atherosclerotic abdominal aortic aneurysm. Although frank rupture often is easily diagnosed on CT, other findings such as a hyperattenuating crescent, discontinuous intimal calcium, and draping of the aorta are subtle signs of aneurysm instability. A true aneurysm should be distinguished from a rapidly growing, saccular pseudoaneurysm in the setting of infectious aortitis, as treatment strategy differs. Acute aortic syndrome involving the abdominal aorta, such as dissection and intramural hematoma, often is an extension of thoracic aortic disease, whereas penetrating atherosclerotic ulcers occasionally involve only the abdominal aorta. The goal of treating acute aortic pathology is to repair and prevent rupture, as well as restore and maintain perfusion of the lower extremities, kidneys, and mesentery. However, both open and endovascular repair of the abdominal aorta may become acutely complicated, resulting in compromise of these goals. Examples include aortoenteric fistula, endoleak, anastomotic pseudoaneurysm, graft infection, and thrombosis or kinking of a stent graft resulting in ischemia of the limbs and mesentery.

Influencia de la actividad inflamatoria del trombo mural en los pacientes con aneurisma de aorta abdominal con reparación endoluminal

IntroductionThe pathophysiological mechanisms that are involved in the growth of abdominal aortic aneurysms (AAA) are multifactorial, and include inflammatory changes, as well as haemostatic and endothelial dysfunctions and, the classic atherosclerotic risk factors. The persistence of a biologically active mural thrombus and the aneurysmal sac, as well as the possible development of type 2 endoleaks, can be the origin of the activation of inflammatory mediators, the consequences of which are unknown. The aim of this study is to define a predictive model of complications after endoluminal repair of abdominal aortic aneurysm in the short and medium-term using clinical, serological, and anatomical variables. Material and methodsA total of 50 hospital patients with asymptomatic atherosclerotic AAA were included in the study between January 2016 and November 2016, in the Angiology and Vascular Surgery Department of the Hospital Clínico Universitario de Valladolid. Clinical data were collected (age, gender, cardiovascular risk factors, comorbidity, medication), baseline AAA diameter, aortic growth at 6 months, as well as baseline C-reactive protein levels, interleukin-2 (IL2), IL6 and homocysteine, preoperatively, 7 days postoperatively, and 6 months later. The patients had an angioCT scan in the immediate postoperative period, and at 6 months. ResultsA mean growth in diameter of 6.18mm was observed in the AAA with a leak, while the correctly pressurised AAA showed a decrease of 4.69mm in their mean diameter, with this difference being statistically significant (P=.001). As regards the changes in the thrombus of the aneurysmal sac, in patients with AAA with a leak the thrombus increased by a mean of 7.74mm, while patients with AAA correctly sealed and without leakage only increased by 3.08mm, with this difference being statistically significant (P=.027). A statistically significant relationship was observed between the change in the size of the post-EVAR aneurysm and the plasma levels of CRP and homocysteine at 7 days, and of the change in the size of the intra-aortic thrombus and the plasma levels of IL2 at 7 days and at 6 months. ConclusionsThe biomarker patterns studied in the short and medium term after EVAR should be considered as indicators of an active inflammation process that exerts its influence on aortic remodelling.

Postoperative initial 2-day blood pressure management facilitates the shrinkage of abdominal aortic aneurysm after endovascular aneurysm repair by reducing the incidence of type II endoleak

ObjectiveThe aim of this study was to evaluate the effect of initial 2-day blood pressure management (BPM) after endovascular aneurysm repair (EVAR) for the incidence of subsequent type II endoleak (T2E) and shrinkage of abdominal aortic aneurysm (AAA) sac diameter. MethodsWe reviewed 136 patients who underwent EVAR for atherosclerotic AAA between July 2008 and July 2014 with one of three stent grafts (Excluder [W. L. Gore & Associates, Flagstaff, Ariz], Powerlink [Endologix Inc, Irvine, Calif], and Endurant [Medtronic Vascular, Santa Rosa, Calif]). Starting from 2013, the mean blood pressure of 76 participating patients (treatment group) was maintained at 75 to 90 mm Hg for the initial 48 hours after EVAR. The incidence of T2E at 7 days and AAA sac diameter 12 months after EVAR were evaluated using computed tomography scanning. The results so obtained were then compared with those of the control group composed of 60 consecutive patients who underwent EVAR before 2013. ResultsThe incidence of T2E at 7 days was significantly lower in patients who received treatment (treatment group, 19.7%; control group, 40.0%; P = .013), and AAA sac diameter at 12 months in the treatment group had a mean decrease of 5.1 mm compared with the mean 2.2 mm in the control group (P = .004). In multivariate regression analysis, BPM was significantly related to the reduction of incidence of T2E at 7 days (odds ratio, 0.31; P = .007) and a decrease in AAA sac diameter at 12 months (P = .005). In addition, although the use of Endurant had less effect, the use of Excluder under controlled blood pressure conditions improved the incidence of T2E from 80% to 23% compared with those under normal postoperative management (P = .001). ConclusionsThe initial 2-day postoperative BPM might have positive effects, such as lower incidence of T2E and facilitation of AAA sac shrinkage.

Outcomes after Open Surgery for Inflammatory Abdominal Aortic Aneurysm: A 10-Year Single-Center Experience

Inflammatory abdominal aortic aneurysms (IAAAs) are rare clinical entitieswith an exaggerated inflammatory component. The aim of this study is to report outcomes of a single-center 10-year experience in open surgical management of IAAA and to compare the results with noninflammatory, atherosclerotic abdominal aortic aneurysms (non-IAAAs). We retrospectively reviewed the medical records of 18 patients with IAAA selected out of patients with AAA who underwent open surgery in the Department of Vascular and Endovascular Surgery at the University Hospital Dusseldorf from January 2006 to December 2015. These patients were matched with controls, selected from a prospectively retained database of patients with AAA undergoing open surgery during the study period. A 1:2 case-control match regarding age, gender, and year of treatment was performed. We analyzed both groups for preoperative parameters, intraoperative findings, and early postoperative outcomes. The 2 groups showed considerable similarities with no significant differences in the clinical features. Both groups outlined comparable aneurysm size (62 vs. 56mm); however, the mean preoperative C-reactive protein was found to be significantly elevated in the study group (mean value: 2.6 vs. 0.9mg/dL, P<0.05). Most patients were operated using a standard transperitoneal median laparotomy approach; only 1 patient of each group was operated using a left retroperitoneal approach. There was no significant difference in operation time (190 vs. 194 min) and 30-day mortality 0%. The in-hospital mortality was 11% in the study group and 0% in the control group. We found a significant higher complication rate in the study group 10 (56%) vs. 12 (33%). The major complications were also more frequent in the study group 4 (22%) vs. 6 (16.7%). IAAA showed a statistically significant longer length of intensive care unit and hospital stay when compared with non-IAAA (7 and 20days vs. 2 and 14days, P<0.05). IAAAs outlined a significantly greater transfusion requirement for erythrocytes and fresh frozen plasma than non-IAAA. Open surgical treatment of IAAA guarantees a regression of the inflammatory process in most patients, which was detected through ultrasound in follow-up examination, although the approach to the surgical site is highly demanding. IAAA exhibits clear gender predominance and is associated with significantly higher transfusion requirement, early morbidity, and length of stay.

Abstract 489: A Data Driven Approach to Identify Subtypes of Abdominal Aortic Aneurysm With Distinct Clinical and Genetic Characteristics

Background: Abdominal aortic aneurysm (AAA) is a complex and heterogeneous disorder. We hypothesized that dense phenomapping using electronic health records (EHR) can identify subtypes of AAA with distinct clinical and genetic characteristics. Methods &amp; Results: AAA cases (n=1108) and controls (n=4694) were identified from the Mayo vascular disease biorepository and had available high-density genotyping data. 132 Candidate genetic variants (p &lt; 10E-5) associated with atherosclerotic cardiovascular disease (ASCVD) or AAA were selected from GWAS catalog. Using model-based Gaussian-mixture cluster analysis of 46 clinical features from 6 data domains, 24 data elements, 204 variables (including age, sex, vital signs, laboratory data, medication use, family history), spanning over 20 years of observational time in the EHR, we identified two subtypes of AAA: subtype 1(S1, n=421) with faster AAA growth rate (baseline size adjusted mean difference, 95% CI: 0.013, 0.001 to 0.020 cm / year faster, p = 0.03), higher all-cause mortality (age &amp; sex adjusted hazard ratio, 95% CI: 1.36, 1.09 - 1.70, p &lt; 0.01) than subtype 2 (S2, n=687). As compared with the controls, thyroid disorder / rheumatoid or osteoarthritis / infectious conditions were uniquely associated with increased odds ratio for S1; ASCVD / hyperlipidemia / hypertension were uniquely associated with increased odds ratio for S2. After adjustment for all group-specific diseases, genetic variants in CDKN2B-AS1, NOA1-REST, ERG, ZNF335-MMP9 and SMAD3 were associated with S1 and variants in MMP12, DAB2IP, LHFPL2, LPA, FSTL5 and SORT1 were associated with S2 (all FDR p &lt; 0.05). After adjustment for disease comorbidities and genetic variants differently associated with S1 and S2, the increased risk for all-cause death of S1 than S2 and the difference in AAA expansion rate in subgroups attenuated (Both p-values &gt; 0.09) Conclusions: We identified two subtypes of AAA with different rates of aneurysm expansion and all-cause mortality, which were associated with subtype-specific disease comorbidities and genetic markers, suggesting the potential of leveraging EHR to facilitate individualized medicine in patients with AAA.

The water channel AQP1 is expressed in human atherosclerotic vascular lesions and AQP1 deficiency augments angiotensin II-induced atherosclerosis in mice.

The water channel aquaporin 1 (AQP1) promotes endothelial cell migration. It was hypothesized that AQP1 promotes neovascularization and growth of atherosclerotic plaques. AQP1 immunoreactivity and protein abundance was examined in human and murine atherosclerotic lesions and aortic aneurysms. Apolipoprotein E (ApoE) knockout (-/-) and AQP1-/-ApoE-/- mice were developed and fed Western diet (WD) for 8 and 16weeks to accelerate the atherosclerosis process. In ApoE-/- and AQP1-/-ApoE-/- mice abdominal aortic aneurysms (AAA) were induced by angiotensin II (ANGII) infusion by osmotic minipumps for 4weeks. In human atherosclerotic lesions and AAA, AQP1 immunoreactive protein was associated with intralesional small vessels. In ApoE-/- mouse aorta, APQ1 mRNA levels were increased with time on WD (n=7-9, P<0.003). Both in murine lesions at the aortic root and in the abdominal aortic aneurysmal wall, AQP1 immunoreactivity was associated with microvascular structures. The atherosclerotic lesion burden was enhanced significantly in ANGII-infused AQP1-/-ApoE-/- mice compared with ApoE-/- mice, but neither incidence nor progression of AAA was different. The aortic lesion burden increased with time on WD but was not different between ApoE-/- and AQP1-/-ApoE-/- mice at either 8 or 16weeks (n=13-15). Baseline blood pressure and ANGII-induced hypertension were not different between genotypes. AQP1 is expressed in atherosclerotic lesion neovasculature in human and mouse arteries and AQP1 deficiency augments lesion development in ANGII-promoted atherosclerosis in mice. Normal function of AQP1 affords cardiovascular protection.

Long-Term Outcomes of Open Repair of Inflammatory and Atherosclerotic Abdominal Aortic Aneurysms

Background: Abdominal aortic aneurysms (AAA) are a common vascular disease mostly affecting those over the age of 65 years. Open surgical repair (OSR) is considered the gold standard for the treatment of AAA, however longterm mortality and morbidity still remain high in patients with inflammatory AAA, when compared to atherosclerotic AAA. The aim of this study was to evaluate long-term outcomes of both inflammatory and atherosclerotic AAA after OSR. Methods: Out of 837 aortic interventions, 149 patients were identified as having undergone open surgical repair for AAA between 2003 and 2013. Of the 149 patients, histopathological data was available for 92 patients with open AAA repair. Kaplan-Meier curves were analysed to evaluate probability of survival. Results: Patients with inflammatory AAA were younger (70 years) by an average of 2 years compared to atherosclerotic AAA (72 years). Morbidity and length of intensive care stay were insignificantly different in both groups. Inflammatory AAA were associated with higher all cause survival rate (82%) compared to atherosclerotic AAA (68%) (P=0.008) after ten years. Conclusion: There was no difference in clinical outcomes between both atherosclerotic AAA and inflammatory AAA, which is due to the technique used. IAAA were associated with lower mortality rates and improved all cause survival at ten years post open surgical repair.

Aorto-duodenal fistula: a rare but serious complication of gastrointestinal hemorrhage. A case report.

A primary aortoduodenal fistula (PADF) is a rare cause of gastrointestinal bleeding that is difficult to diagnose (and sometimes not diagnosed until a laparotomy.) A PADF is associated with high mortality if undiagnosed and untreated (the mortality rate of nearly 100% in the absence of a surgical intervention). While this condition is extremely rare with an incidence rate at autopsy of 0.04% to 0.07%, a secondary ADF occurs much more commonly (the post-operative incidence of 0.5% to 2.3%) and is due to prior aortic surgery and/or the placement of a synthetic aortic graft. It should be considered in any elderly patient who presents with upper gastrointestinal bleeding in the context of a known abdominal aortic aneurysm or without it when no identifiable source of bleeding is found. We present an autopsy case of a 59-year-old man with no history of an abdominal aortic aneurysm who presented with intermittent massive gastrointestinal bleeding. The autopsy revealed a pinhole fistula. It was identified between an atherosclerotic abdominal aortic aneurysm and the lower horizontal part of the duodenum. Our case indicates that the aortoenteric fistula can result in fatal gastrointestinal bleeding. This case is unique in that the fistula formed as a result of a complex atherosclerotic abdominal aorta and a localized necrotizing granulomatous aortitis the etiology of which was not clear.