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Prediction of abdominal aortic aneurysm (AAA) rupture is a challenging issue. Small noncoding microRNAs (miRNAs) are potent regulators of gene expression and are considered as valuable circulating biomarkers. Recently, [The level of 372 miRNAs was evaluated by polymerase chain reaction array in plasma from 35 AAA patients displaying no FDG uptake (A0) and 22 patients with a positive PET uptake (A+). The modulated miRNAs were validated by quantitative polymerase chain reaction and measured in aneurysmal tissues from both groups of patients.Six circulating miRNAs were found significantly modulated in A+ vs A0 patients. They were significantly correlated not only between them but also with the intensity of FDG uptake. Two of them correlated also with the AAA diameter. These miRNAs displayed significant discriminating power between the A+ and A0 groups as determined by receiver operating characteristic curves. Three downregulated circulating miRNAs (miR-99b-5p, miR-125b-5p, and miR-204-5p) were also significantly reduced in the aneurysmal tissue, specifically in the FDG-uptake site, compared with a negative zone in the same aneurysm and with A0 aneurysms. They were further significantly inversely correlated with the expression, at the positive uptake site, of some of their potential gene targets, most notably matrix metalloproteinase 13.Six miRNAs were identified as potential new circulating biomarkers of PET+ AAA. Three of these were similarly modulated in the metabolically active aneurysmal wall and might be directly involved in AAA instability.

Aortic dissection is a life-threatening condition caused by a tear in the intimal layer of the aorta or bleeding within the aortic wall, resulting in the separation (dissection) of the layers of the aortic wall. Aortic dissection is most common in those 65-75 years of age, with an incidence of 35 cases per 100,000 people per year in this population. Other risk factors include hypertension, dyslipidaemia and genetic disorders that involve the connective tissue, such as Marfan syndrome. Swift diagnostic confirmation and adequate treatment are crucial in managing affected patients. Contemporary management is multidisciplinary and includes serial non-invasive imaging, biomarker testing and genetic risk profiling for aortopathy. The choice of approach for repairing or replacing the damaged region of the aorta depends on the severity and the location of the dissection and the risks of complication from surgery. Open surgical repair is most commonly used for dissections involving the ascending aorta and the aortic arch, whereas minimally invasive endovascular intervention is appropriate for descending aorta dissections that are complicated by rupture, malperfusion, ongoing pain, hypotension or imaging features of high risk. Recent advances in the understanding of the underlying pathophysiology of aortic dissection have led to more patients being considered at substantial risk of complications and, therefore, in need of endovascular intervention rather than only medical or surgical intervention.

Background Abdominal aortic aneurysm (AAA) is a major cause of preventable deaths in older patients. Oxidative stress has been suggested to play a key role in the pathogenesis of AAA. However, only few studies have been conducted to evaluate the blood oxidative stress status of AAA patients. Methods and results Twenty seven AAA patients (mean age of 70 years) divided into two groups according to AAA size (≤50 or >50 mm) were compared with an age-matched group of 18 healthy subjects. Antioxidants (vitamins C and E, β-carotene, glutathione, thiols, and ubiquinone), trace elements (selenium, copper, zinc, and copper/zinc ratio) and markers of oxidative damage to lipids (lipid peroxides, antibodies against oxidized patients, and isoprostanes) were measured in each subject. The comparison of the three groups by ordinal logistic regression showed a significant decrease of the plasma levels of vitamin C (P = 0.011), α-tocopherol (P = 0.016) but not when corrected for cholesterol values, β-carotene (P = 0.0096), ubiquinone (P = 0.014), zinc (P = 0.0035), and of selenium (P = 0.0038), as AAA size increased. By contrast, specific markers of lipid peroxidation such as the Cu/Zn ratio (P = 0.046) and to a lesser extent isoprostanes (P = 0.052) increased. Conclusion The present study emphasizes the potential role of the oxidative stress in AAA disease and suggests that an antioxidant therapy could be of interest to delay AAA progression.

Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recognized emerging entity characterized by chronic fibroinflammation that can affect every organ but rarely affects the cardiovascular system. We report a rare case of IgG4-RSD involving an aortic valve that resulted in rapid progression of an aortic valvular stenosis and was successfully treated by aortic valve replacement and corticosteroids.

Aneurysm of the abdominal aorta (AAA) is a particular, specifically localized form of atherothrombosis, providing a unique human model of this disease. The pathogenesis of AAA is characterized by a breakdown of the extracellular matrix due to an excessive proteolytic activity, leading to potential arterial wall rupture. The roles of matrix metalloproteinases and plasmin generation in progression of AAA have been demonstrated both in animal models and in clinical studies. In the present review, we highlight recent studies addressing the role of the haemoglobin-rich, intraluminal thrombus and the adventitial response in the development of human AAA. The intraluminal thrombus exerts its pathogenic effect through platelet activation, fibrin formation, binding of plasminogen and its activators, and trapping of erythrocytes and neutrophils, leading to oxidative and proteolytic injury of the arterial wall. These events occur mainly at the intraluminal thrombus–circulating blood interface, and pathological mediators are conveyed outwards, where they promote matrix degradation of the arterial wall. In response, neo-angiogenesis, phagocytosis by mononuclear cells, and a shift from innate to adaptive immunity in the adventitia are observed. Abdominal aortic aneurysm thus represents an accessible spatiotemporal model of human atherothrombotic progression towards clinical events, the study of which should allow further understanding of its pathogenesis and the translation of pathogenic biological activities into diagnostic and therapeutic applications.

Contains fulltext : 70663.pdf (Publisher’s version ) (Closed access) Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.

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. \ud 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.

Prediction of abdominal aortic aneurysm (AAA) rupture by specific biomarkers is a challenging issue in the field of vascular diseases. Small non-coding RNAs, miRNAs, are potent post-transcriptional regulators of gene expression and were found to be present in blood and to represent valuable biomarkers for a variety of diseases, notably in cancer. Recently, we showed that a positive uptake of 18F-fluorodeoxyglucose (FDG) in the aneurysmal wall observed by positron emission tomography (PET) was correlated with a higher instability of the wall which could lead to its rupture. Identifying circulating miRNAs correlated with a positive PET could help discriminating patients at higher risk of rupture. The expression level of 372 miRNAs was evaluated by using the miScript PCR system (Qiagen) in the plasma of 45 AAA patients among whom 24 had no FDG uptake (A0) and 21 displayed a positive PET (A+). In a first approach, 4 pools of plasma samples from the A0 and the A+ groups were analyzed. 14 miRNAs were found significantly modulated (8 downregulated and 6 upregulated, p In conclusion, 8 circulating miRNAs might represent a new signature of PET+ AAA, at high risk of rupture. Moreover, 2 of them are significantly downregulated in the metabolically active aneurysmal wall prone to rupture. It is noteworthy that a validated target of miR-125b-5p is MMP13, a collagenase that we previously showed to be largely increased in the positive FDG uptake site of adventitia and that could be potentially involved in the ultimate degradation of collagen leading to aneurysmal rupture.

Objectives: To evaluate imaging changes occurring in a rat model of elastase-induced abdominal aortic aneurysm (AAA), with emphasis on the intraluminal thrombus (ILT) occurrence. Methods: The post-induction growth of the AAA diameter was characterized using ultrasound in 22 rats. ILT was reported on 13 rats that underwent 14 magnetic resonance imaging (MRI) 2-18 days post-surgery, and on 10 rats that underwent 18 fluoro-deoxyglucose (FDG) positron emission tomography (PET)/microcomputed tomography examinations 2-27 days post-surgery. Logistic regressions were used to establish the evolution with time of AAA length, diameter, ILT thickness, volume, stratification, MRI and FDG PET signalling properties, and histological assessment of inflammatory infiltrates. Results: All of the following significantly increased with time post-induction (p

Background Abdominal aortic aneurysms (AAAs) are characterized by histologic signs of chronic inflammation, destructive remodeling of extracellular matrix, and depletion of vascular smooth muscle cells. We investigated the process of extracellular matrix remodeling by performing a genetic association study with polymorphisms in the genes for matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and structural extracellular matrix molecules in AAA. Our hypothesis was that genetic variations in one or more of these genes contribute to greater or lesser activity of these gene products, and thereby contribute to susceptibility for developing AAAs. Methods DNA samples from 812 unrelated white subject (AAA, n=387; controls, n=425) were genotyped for 14 polymorphisms in 13 different candidate genes: MMP1(nt-1607), MMP2(nt-955), MMP3(nt-1612), MMP9(nt-1562), MMP10(nt+180), MMP12(nt-82), MMP13(nt-77), TIMP1(nt+434), TIMP1(rs2070584), TIMP2(rs2009196), TIMP3(nt-1296), TGFB1(nt-509), ELN(nt+422), and COL3A1(nt+581). Odds ratios and P values adjusted for gender and country of origin using logistic regression and stratified by family history of AAA were calculated to test for association between genotype and disease status. Haplotype analysis was carried out for the two TIMP1 polymorphisms in male subjects. Results Analyses with one polymorphism per test without interactions showed an association with the two TIMP1 gene polymorphisms (nt+434, P = .0047; rs2070584, P = .015) in male subjects without a family history of AAA. The association remained significant when analyzing TIMP1 haplotypes (χ 2 P = .014 and empirical P = .009). In addition, we found a significant interaction between the polymorphism and gender for MMP10 ( P = .037) in cases without a family history of AAA, as well as between the polymorphism and country of origin for ELN ( P = .0169) and TIMP3 ( P = .0023) in cases with a family history of AAA. Conclusions These findings suggest that genetic variations in TIMP1, TIMP3, MMP10, and ELN genes may contribute to the pathogenesis of AAAs. Further work is needed to confirm the findings in an independent set of samples and to study the functional role of these variants in AAA. It is noteworthy that contrary to a previous study, we did not find an association between the MMP9 (nt-1562) polymorphism and AAA, suggesting genetic heterogeneity of the disease. Clinical Relevance Abdominal aortic aneurysms (AAAs) are an important cardiovascular disease, but the genetic and environmental risk factors, which contribute to individual's risk to develop an aneurysm, are poorly understood. Histologically, AAAs are characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells. We hypothesized that genes involved in these events could harbor changes that make individuals more susceptible to developing aneurysms. This study identified significant genetic associations between DNA sequence changes in tissue inhibitor of metalloproteinase 1 (TIMP1), TIMP3, matrix metalloproteinase 10 (MMP10) and elastin (ELN) genes, and AAA. The results will require confirmation using an independent set of samples. After replication it is possible that these sequence changes in combination with other risk factors could be used in the future to identify individuals who are at increased risk for developing an AAA.

Background— Abdominal aortic aneurysm (AAA) is a relatively common disease, with 1% to 2% of the population harboring aneurysms. Genetic risk factors are likely to contribute to the development of AAAs, although no such risk factors have been identified. Methods and Results— We performed a whole-genome scan of AAA using affected-relative-pair (ARP) linkage analysis that includes covariates to allow for genetic heterogeneity. We found strong evidence of linkage (logarithm of odds [LOD] score=4.64) to a region near marker D19S433 at 51.88 centimorgans (cM) on chromosome 19 with 36 families (75 ARPs) when including sex and the number of affected first-degree relatives of the proband (N aff ) as covariates. We then genotyped 83 additional families for the same markers and typed additional markers for all families and obtained a LOD score of 4.75 ( P =0.00014) with sex, N aff , and their interaction as covariates near marker D19S416 (58.69 cM). We also identified a region on chromosome 4 with a LOD score of 3.73 ( P =0.0012) near marker D4S1644 using the same covariate model as for chromosome 19. Conclusions— Our results provide evidence for genetic heterogeneity and the presence of susceptibility loci for AAA on chromosomes 19q13 and 4q31.

Horton disease or giant-cell arteritis (GCA) is a chronic systemic vasculitis involving typically medium and large arteries. Giant-cell arteritis is a panarteritis characterized by a granulomatous inflammation, with lymphocytes, macrophages, and multinucleated giant cells related to autoimmune T-cell reactivity.1 Compared with conventional imaging tools (ultrasound, computed tomography (CT), MRI, and contrast angiography) that provide anatomic and morphological information, recent available imaging techniques such as positron emission tomography (PET)/CT provide metabolic assessment of the arterial wall. During the early 2000s, Sakalihasan et al2 observed a close correlation between clinically unstable abdominal aortic aneurysms and increased uptake of 18F-fluoro-2-deoxy-d-glucose (FDG) in the aneurysmal wall. A few years later, Hautzel et al3 studied the assessment of giant-cell arteritis with PET/CT. We describe a case of Horton disease involving the thoracic aorta and complicated with acute aortic dissection in a woman with a previous diagnosis of thoracic aortic aneurysm. In July 2011, a 66-year-old woman was referred to a cardiology center for evaluation of a recent mild hypertension related to use of high doses of corticosteroids. In December 2010, she had developed severe headache, rapid loss of weight, and elevation of sedimentation rate as high as 120 mm. Horton disease was diagnosed in April 2011 on temporal artery biopsy. During the first cardiologic examination, …

Objective: Significant alterations of the vascular wall occurs in abdominal aortic aneurysm (AAA) and atherosclerotic occlusive disease (AOD) that ultimately may lead to either vascular rupture or obstruction. These modifications have been ascribed to one or a group of proteases, their inhibitors or to the matrix macromolecules involved in the repair process without considering the extent of the observed variations. Methods: The mRNA steady-state level of a large spectrum of proteolytic enzymes (matrix metalloproteinases: MMP-1, -2, -3, -8, -9, -11, -12, -13, -14; urokinase plasminogen activator: u-PA), their physiological inhibitors (tissue inhibitors of MMPs: TIMP-1, -2, -3; plasminogen activator inhibitor: PAI-1) and that of structural matrix proteins (collagens type I and III, decorin, elastin, fibrillins 1 and 2) was determined by RT-PCR made quantitative by using a synthetic RNA as internal standard in each reaction mixture. The profile of expression was evaluated in AAA ( n = 7) and AOD ( n = 5) and compared to non-diseased abdominal (CAA, n = 7) and thoracic aorta (CTA, n = 5). Results : The MMPs -8, -9, -12 and -13 mostly associated with inflammatory cells were not or barely detected in CAA and CTA while they were largely and similarly expressed in AAA and AOD. Expression of protease inhibitors or structural proteins were only slightly increased in both pathological conditions with the exception of elastin which was reduced. The main significant difference between AAA and AOD was a lower expression of TIMP-2 and PAI-1 in the aneurysmal lesions. Conclusions: The remodeling of the aortic wall in AAA and AOD involves gene activation of a large and similar spectrum of proteolytic enzymes while the expression of two physiological inhibitors, TIMP-2 and PAI-1, is significantly lower in AAA compared to AOD. The repair process in the aneurysmal disease seems similar to that of the occlusive disease.

Background Prediction of abdominal aortic aneurysm (AAA) rupture is a challenging issue. Small noncoding microRNAs (miRNAs) are potent regulators of gene expression and are considered as valuable circulating biomarkers. Recently, [ 18 F]fluorodeoxyglucose (FDG) uptake detected by positron emission tomography (PET) in AAA was correlated with cellular and molecular alterations involved in wall instability and its potential rupture. Our study aimed at identifying circulating miRNAs correlated with a positive PET that could help discriminate patients at high risk of rupture. Methods The level of 372 miRNAs was evaluated by polymerase chain reaction array in plasma from 35 AAA patients displaying no FDG uptake (A0) and 22 patients with a positive PET uptake (A+). The modulated miRNAs were validated by quantitative polymerase chain reaction and measured in aneurysmal tissues from both groups of patients. Results Six circulating miRNAs were found significantly modulated in A+ vs A0 patients. They were significantly correlated not only between them but also with the intensity of FDG uptake. Two of them correlated also with the AAA diameter. These miRNAs displayed significant discriminating power between the A+ and A0 groups as determined by receiver operating characteristic curves. Three downregulated circulating miRNAs (miR-99b-5p, miR-125b-5p, and miR-204-5p) were also significantly reduced in the aneurysmal tissue, specifically in the FDG-uptake site, compared with a negative zone in the same aneurysm and with A0 aneurysms. They were further significantly inversely correlated with the expression, at the positive uptake site, of some of their potential gene targets, most notably matrix metalloproteinase 13. Conclusions Six miRNAs were identified as potential new circulating biomarkers of PET+ AAA. Three of these were similarly modulated in the metabolically active aneurysmal wall and might be directly involved in AAA instability.

Cervical artery dissection (CeAD) is a rare condition. One of the causes is the vascular type of Ehlers-Danlos syndrome (vEDS). A novel missense mutation in COL3A1 was found in a young patient with CeAD as the single manifestation of vEDS. This is a heterozygous c.953G > A mutation in exon 14, disrupting the normal Gly-X-Y repeats of type III procollagen, by converting glycine to aspartic acid. (C) 2015 Elsevier Masson SAS. All rights reserved.

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.

Endovascular aortic repair (EVAR) has been applied to abdominal aortic aneurysm (AAA) to decrease and prevent morbidity and mortality due to open surgery. However, this therapeutic approach may lead to complications such as occurrence of endoleaks which may result in rupture of the aneurysm. Decisions for complementary treatment after EVAR to prevent aneurysm rupture are based on endoleak characterization and aortic diameter evolution. The presence of endoleak or enlarging diameter is however not always predictive of rupture. Recent reports support the view that 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) provides unique information on cellular metabolic activity thought to drive aneurysm expansion and rupture. We evaluated if FDG/PET could predict the outcome of aneurysm repaired by endoprosthesis. A cohort of 56 AAA patients (55 male; mean age of 74.6 years), treated by EVAR, underwent one or several PET/CT before and/or after surgery with a total number of 108 examinations. The quantification analysis of FDG uptake was not correlated to the AAA diameter but was strongly correlated with the presence of endoleak (55% of endoleak in patients with significant FDG uptake (PET+) versus 25% in PET0). Moreover, the PET+ AAA presented symptoms such as increasing diameter of aneurysmal sac (64% in PET+ versus 33% in PET0). On the other hand, two PET+ patients underwent conversion for open surgery for rapid growth and rupture with leaking. These outcomes did not occur among the PET0 patients. Increased circulating levels of fibrinolytic factors (D-dimers, thrombin/anti-thrombin and plasmin/anti-plasmin complexes) and inflammatory cytokines IL6 and IL8, were found in patients with endoleak while the collagenase MMP1 was largely decreased. Finally, two other MMPs, MMP12 and MMP13 were correlated with the uptake level of FDG. Altogether, these results suggest that the presence of endoleak is associated with an activation of the fibrinolytic pathway and PET positivity induces factors involved in the extracellular matrix remodeling leading to instability of the wall and its rupture. This study suggests that PET/CT might predict the negative outcome of EVAR and represent a beneficial tool for patient management.

From January 1990 to December 1997, the authors observed 13 cases of fibromuscular dysplasia of the internal carotid artery. Four patients presented transient ischemic attacks, one amaurosis fugax, two suffered from a minor stroke, four had non-focalized ischemic cerebral symptoms and two were asymptomatic. At angiography, all patients showed a typical image of "string of beads". Seven patients were operated on. Six had endoluminal graduated dilatation, with rigid dilators up to 4.5 mm, associated with thrombendarterectomy of the bifurcation in three and to correction of a kink in one case. In one case a venous interposition graft was done to exclude a saccular microaneurysm of the dysplasic internal carotid artery. In another case, backflow was insufficient after endoluminal dilatation, and a long venous patch allowed to restitute a normal vascular lumen. There was neither postoperative mortality nor stroke. Six patients, asymptomatic or with non focalized symptoms, were treated medically. During a mean follow-up of 47 months, only one of the 13 patients developed a transient ischemic attack; the patient had not been operated on and received only medical treatment. Prevalence, etiopathology, diagnosis and management of fibromuscular dysplasia of the internal carotid artery are discussed. Fibromuscular dysplasia is a rare cause of cerebral ischemia. For asymptomatic lesions, a conservative approach seems appropriate. Surgery is only to be considered for symptomatic lesions. Surgical graduated endoluminal dilatation, where necessary combined with standard endarterectomy of the carotid bifurcation, is a safe, efficient and durable operation. Some complex cases of fibromuscular dysplasia may necessitate patch insertion or excision and graft interposition.

Aneurysms are characterized by dilation, i.e. expansion and thinning of all the arterial wall layers, which is accompanied by remodeling of the connective tissue. Genes involved in the regulation of tissue remodeling are therefore candidate genes. We analyzed TIMP1 and TIMP2 coding sequences in 12 individuals with abdominal aortic aneurysms (AAA), one individual with AAA and intracranial aneurysms (IA), four individuals with IA and two clinically unaffected individuals. We identified two nucleotide variants in both the TIMP1 and the TIMP2 coding sequences. All differences occurred in the third base positions of codons and were neutral polymorphisms. A significant difference was observed in the frequency of TIMP2 nt 573 polymorphism between 168 alleles from AAA patients and 102 control alleles.

The decision on whether to operate or not abdominal aortic aneurysms (AAA) in elderly depends on the relative risk of the operation versus the natural course of the unoperated AAA. From January 1984 to December 996, 138 patients, aged 80 years and older, were referred to our department for an aneurysm of 40 mm or more (transverse diameter) of the infrarenal abdominal aorta (95 asymptomatic, 15 painful, and 28 ruptured AAA). For 58 patients with asymptomatic AAA, operation was denied at referral because of transverse diameter less than 50 mm (n = 21), patient refusal (n = 10) or unacceptable operative risk or poor general condition (n = 27). Thirty-four of these observed AAA were ultimately operated after a mean delay of 41 months because of aneurysm enlargement (n = 15), aneurysm tenderness (n = 6) or rupture (n = 13). Overall, 52 patients had immediate (n = 37) or delayed (n = 15) elective repair of their AAA, with an in-hospital mortality of 5.7%. Urgent operation was done for 21 patients with a painful AAA. Six patients died at hospital (28% mortality rate). Emergent surgery was applied to 41 patients with ruptured AAA (including 13 AAA who ruptured during surveillance). The operative mortality in this subgroup attained 68%. Follow-up for the 77 survivors and the 24 non-operative patients averaged 43 months. The 5-year survival (operative mortality included) is 47% for electively operated patients, 30% for urgently and 20% for emergently operated patients. For comparison, the 5-year survival of an age and sex matched Belgian population is 63%. For the 24 medically followed AAA, the 5-year survival was 33%. In six cases, the cause of death was rupture of the AAA. Of the 58 patients for whom operation was initially not considered, 19 (33%) presented AAA rupture (13 operated in emergency and 6 who never came to surgery). The operative outcome of AAA repair in octogenarians is less favourable than in the younger age group (3.6% mortality after elective repair, 44% after operation for AAA rupture, according to our institution data). The authors conclude that AAA surgery should not be denied to octogenarians on the basis of advanced age alone. They recommend a straightforward surgery for otherwise healthy octogenarians with AAA of 50 mm diameter, surveillance up to 60 mm for high-risk patients and no surgery for unfit, bedridden or demented patients.

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Primary tumors of the aorta are extremely rare and the diagnosis is made most often after surgery or autopsy. Because clinical symptoms of abdominal sarcoma are similar to those of occlusive or aneurysmal disease, aortic sarcomas are frequently mistaken for these lesions. The imaging findings are frequently nonspecific and therefore do not allow a definitive preoperative diagnosis. We report a case of an epithelioid angiosarcoma in the vessel wall of an abdominal aortic aneurysm.

Background The objectives were to answer the following questions with the help of a well-characterized population in Liege, Belgium: 1) what percentage of patients with abdominal aortic aneurysm (AAA) have a positive family history for AAA? 2) what is the prevalence of AAAs among relatives of patients with AAA? and 3) do familial and sporadic AAA cases differ in clinical characteristics? Methods Patients with unrelated AAA diagnosed at the Cardiovascular Surgery Department, University Hospital of Liege, Belgium, between 1999 and 2012 were invited to the study. A detailed family history was obtained in interviews and recorded using Progeny software. We divided the 618 patients into 2 study groups: group I, 296 patients with AAA (268; 91% men) were followed up with computerized tomography combined with positron emission tomography; and group II, 322 patients with AAA (295; 92% men) whose families were invited to ultrasonographic screening. Results In the initial interview, 62 (10%) of the 618 patients with AAA reported a positive family history for AAA. Ultrasonographic screening identified 24 new AAAs among 186 relatives (≥50 years) of 144 families yielding a prevalence of 13%. The highest prevalence (25%) was found among brothers. By combining the number of AAAs found by ultrasonographic screening with those diagnosed previously the observed lifetime prevalence of AAA was estimated to be 32% in brothers. The familial AAA cases were more likely to have a ruptured AAA than the sporadic cases (8% vs. 2.4%; P Conclusions The findings confirm previously found high prevalence of AAA among brothers, support genetic contribution to AAA pathogenesis, and provide rationale for targeted screening of relatives of patients with AAA.

Autosomal dominant polycystic kidney disease (ADPKD) is a risk factor for several cardiovascular disorders such as intracranial aneurysm or aortic dissection, preferentially occurring at the thoracic or abdominal level. A 47-year-old man suffering from ADPKD had renal transplantation. Sixteen hours after surgery, he presented with left leg pain. Clinical and ultrasound examination revealed thrombosis of the external left iliac artery. Therefore, we decided to perform intra-arterial angiography to evaluate the possibility of an endovascular treatment. Aorto-femorography showed an obstruction of the external left iliac artery that was found during emergency surgery, consecutive to a dissection, which occurred following the surgery for kidney transplantation. The resected segment of the dissected vessel was analyzed by histology. Collagen fibers organization and density in the adventitia and smooth muscle cells density in the media were similar in the dissected and a normal artery from a healthy donor. By contrast, an almost complete disappearance and fragmentation of elastic lamellae were observed in the media of the dissected artery, most likely responsible for the weakening of the arterial wall and its dissection. Association between ADPKD and single dissection of the iliac artery has been rarely reported. Relationship between inactivation of polycystin/PKD genes and elastic fibers degradation through elevated TGFβ signaling and matrix metalloproteinase 2 (MMP2) elastolytic activity, as recently reported in ADPKD, would be worth investigating.

Purpose: The consistent observation of a reduction of the elastin concentration in abdominal aortic aneurysms (AAAs) has led us to investigate in AAA specimens two metalloproteinases that display elastase activity, MMP 2 (gelatinase A/72 kDa) and MMP 9 (gelatinase B/92 kDa). Methods: Samples of full-thickness aortic wall, adherent thrombus, and serum were collected in 10 patients with AAAs. Samples of normal aortic wall and serum were taken from 6 age-matched control patients. Quantitative gelatin-zymography and gelatinolytic soluble assays after acetyl-phenyl mercuric acid activation were performed on serum and tissue extracts, and the results were expressed in units on a comparative wet-weight basis. Histologic analysis was performed in parallel to score the inflammatory infiltrate. Results: The luminal and parietal parts of the thrombus contained, respectively, 20- and 10-fold more gelatinolytic activity than the serum. The predominate form was MMP 9 . Although the total gelatinolytic activity was in the same range both in AAAs and in normal walls, a significantly higher proportion of MMP 9 was found in the aneurysmal aortic walls. Furthermore, a significant proportion of MMP 9 was under its processed active form, which was never observed in normal samples. A significantly higher proportion of MMP 2 was also present as processed active form in AAA wall. This latter parameter positively correlated with the inflammatory score. Conclusions: The presence of activated MMP 9 and MMP 2 might contribute to the degradation of the extracellular matrix proteins that occurs during the development of aneurysms. (J Vasc Surg 1996;24:127-33.)

The current state of research and treatment on aortic diseases was discussed in the “3rd International Meeting on Aortic Diseases” (IMAD3) held on October 4–6, 2012, in Liège, Belgium. The 3-day meeting covered a wide range of topics related to thoracic aortic aneurysms and dissections, abdominal aortic aneurysms, and valvular diseases. It brought together clinicians and basic scientists and provided an excellent opportunity to discuss future collaborative research projects for genetic, genomics, and biomarker studies, as well as clinical trials. Although great progress has been made in the past few years, there are still a large number of unsolved questions about aortic diseases. Obtaining answers to the key questions will require innovative, interdisciplinary approaches that integrate information from epidemiological, genetic, molecular biology, and bioengineering studies on humans and animal models. It is more evident than ever that multicenter collaborations are needed to accomplish these goals.

With the improvement of survival rates following cardiac transplantation, the probability of recipients developing extracardiac disease is increased. Three cases are reported of abdominal aortic aneurysm successfully operated on in cardiac allograft recipients 1 to 4 years after transplantation. Indications for transplantation were valvular, idiopathic and ischaemic cardiomyopathy. Post-transplant hypertension and hyperlipidaemia may have played a role in the rapid growth of the aneurysms. Cardiac function and the incidence of graft atherosclerosis were assessed before surgery by coronary angiography. All three patients were discharged from hospital. Abdominal aortic aneurysm resection may be a safe procedure in cardiac transplant patients. In view of the rapid increase in the size of the aneurysms in transplanted patients, careful screening should be performed during follow-up.

Purpose: Familial clustering of abdominal aortic aneurysm was first noticed in 1977.Methods: Through questionnaire and phone inquiry, familial data on 324 probands with abdominal aortic aneurysms allowed the establishment of 313 multigenerational pedigrees including 39 with multiple affected patients.Results: There were 276 sporadic cases (264 men, 12 women); 81 cases belonged to multiplex pedigrees (76 men; 5 women). We compared familial and sporadic male cases; the ages at diagnosis were 64.1 ± 7.9 years and 66.0 ± 7.3 years (p < 0.05), respectively, the ages at rupture were 65.4 ± 6.6 years and 75.2 ± 8.6 years (p < 0.001), and the rupture rate was 32.4% and 8.7% (p < 0.001). Survival curves were computed. Relative risk for male siblings of a male patient was 18. We performed a segregation analysis with the mixed model, the most likely explanation for occurrence of abdominal aortic aneurysm in our families was a single gene effect showing dominant inheritance. The frequency of the morbid allele was 1:250, and its age-related penetrance was not higher than 0.4.Conclusion: This analysis indicates the preeminence of genetic factors on multifactorial/environmental effects of the pathogenesis of abdominal aortic aneurysm. (J VASC SURG 1995;21:646-55.)

Atherosclerotic aneurysms limited to the iliac arteries are rare and entail a high risk of rupture. To evaluate the efficacy of prophylactic surgery, we retrospectively studied 15 patients (13 men and two women; mean age 69 years) treated for isolated iliac aneurysms in the Department of Cardiovascular Surgery at the University Hospital of Liege over a period of 18 years. They had a total of 25 aneurysms (20 common iliac and five internal iliac). Six patients were treated electively and nine on an emergency basis for rupture. Five of the emergency patients (33%) died in the early postoperative period (< 30 days); in each case the aneurysm had ruptured and an emergency operation was performed (55.5% mortality in the ruptured iliac aneurysm group). On the other hand, all patients treated electively survived. Our study is comparable to other recent series in the literature, which also reported a high incidence of rupture and death in emergency operations. Prophylactic elective surgery is recommended for iliac aneurysms.

OBJECTIVES: Finite Element (FE) Analysis has been used to estimate Peak Wall Stress (PWS) and Peak Wall Rupture Risk (PWRR) of Abdominal Aortic Aneurysms (AAA). However, these values are not familiar for clinicians. The aim of this study was to introduce a patient specific and clinically applicable biomechanical rupture risk assessment tool that would be easy for Vascular Surgeons to comprehend. METHODS: Clinical data(gender, age, smoking, chronic obstructive lung disease, mean arterial pressure, family history) and CT images were retrospectively gathered from 200(142 male, 44 female) non ruptured AAA patients from 4 different hospitals in Sweden, Belgium and Germany. FE models were created using the diagnostics system A4clinics (VASCOPS, Austria) and the maximum diameter, PWS and PWRR was calculated automatically. Statistical analysis was performed with Mathematica (Wolfram Research Inc, USA). RESULTS: The maximum diameter was normally distributed in males and females and no difference was found between PWS levels in men and women (p=0.091) but the PWRR was higher in women (p=0.005). PWS increased in a linear fashion and PWRR exponentially with diameter. We then related PWRR to the maximum diameters of patients and calculated the Rupture Risk Equvialent Diameter (RRED) as shown in the figure. A PWRR of 0.48 corresponds to an RRED of 55 millimeters. We also found that a RRED of 55 mm corresponds to the rupture risk in a male with a maximum AAA diameter of 58 mm, but in a female the corresponding maximum diameter was only 46mm. CONCLUSIONS: Biomechanical AAA rupture risk assessment integrates risk based on clinical parameters and data from CT images. The RRED expresses this information as a diameter that is comprehensible for clinicians.

Objectives The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components.Background It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with lipoprotein(a) levels and coronary artery disease (CAD), confer susceptibility predominantly via atherosclerosis or thrombosis.Methods The 2 LPA variants were combined and examined as LPA scores for the association with ischemic stroke (and TOAST [Trial of Org 10172 in Acute Stroke Treatment] subtypes) (effective sample size [n(e)] = 9,396); peripheral arterial disease (n(e) = 5,215); abdominal aortic aneurysm (ne = 4,572); venous thromboembolism (ne = 4,607); intracranial aneurysm (ne = 1,328); CAD (n(e) = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588). Results LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio [OR]: 1.27; p = 6.7 X 10(-4)), peripheral artery disease (OR: 1.47; p = 2.9 x 10(-14)), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 x 10(-5)), but not with the ischemic stroke subtypes cardioembolism (OR: 1.03; p = 0.69) or small vessel disease (OR: 1.06; p = 0.52). Although the LPA variants were not associated with carotid intima-media thickness, they were associated with the number of obstructed coronary vessels (p = 4.8 x 10(-12)). Furthermore, CAD cases carrying LPA risk variants had increased susceptibility to atherosclerotic manifestations outside of the coronary tree (OR: 1.26; p = 0.0010) and had earlier onset of CAD (-1.58 years/allele; p = 8.2 x 10(-8)) than CAD cases not carrying the risk variants. There was no association of LPA score with venous thromboembolism (OR: 0.97; p = 0.63) or intracranial aneurysm (OR: 0.85; p = 0.15).Conclusions LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes. (J Am Coll Cardiol 2012; 60: 722-9) (C) 2012 by the American College of Cardiology Foundation

Background Abdominal aortic aneurysm (AAA) is a complex disorder with multiple genetic risk factors. Using affected relative pair linkage analysis, we previously identified an AAA susceptibility locus on chromosome 19q13. This locus has been designated as the AAA1 susceptibility locus in the Online Mendelian Inheritance in Man (OMIM) database. Methods Nine candidate genes were selected from the AAA1 locus based on their function, as well as mRNA expression levels in the aorta. A sample of 394 cases and 419 controls was genotyped for 41 SNPs located in or around the selected nine candidate genes using the Illumina GoldenGate platform. Single marker and haplotype analyses were performed. Three genes (CEBPG, PEPD and CD22) were selected for DNA sequencing based on the association study results, and exonic regions were analyzed. Immunohistochemical staining of aortic tissue sections from AAA and control individuals was carried out for the CD22 and PEPD proteins with specific antibodies. Results Several SNPs were nominally associated with AAA (p < 0.05). The SNPs with most significant p-values were located near the CCAAT enhancer binding protein (CEBPG), peptidase D (PEPD), and CD22. Haplotype analysis found a nominally associated 5-SNP haplotype in the CEBPG/PEPD locus, as well as a nominally associated 2-SNP haplotype in the CD22 locus. DNA sequencing of the coding regions revealed no variation in CEBPG. Seven sequence variants were identified in PEPD, including three not present in the NCBI SNP (dbSNP) database. Sequencing of all 14 exons of CD22 identified 20 sequence variants, five of which were in the coding region and six were in the 3'-untranslated region. Five variants were not present in dbSNP. Immunohistochemical staining for CD22 revealed protein expression in lymphocytes present in the aneurysmal aortic wall only and no detectable expression in control aorta. PEPD protein was expressed in fibroblasts and myofibroblasts in the media-adventitia border in both aneurysmal and non-aneurysmal tissue samples. Conclusions Association testing of the functional positional candidate genes on the AAA1 locus on chromosome 19q13 demonstrated nominal association in three genes. PEPD and CD22 were considered the most promising candidate genes for altering AAA risk, based on gene function, association evidence, gene expression, and protein expression.

To prospectively determine if superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging could help visualize leukocyte phagocytic activities in human abdominal aortic aneurysms (AAAs).This study was approved by the institutional ethics committee; all patients gave informed consent. Preoperative MR imaging data, including unenhanced and SPIO-enhanced T1-, T2*-, and T2-weighted transverse images of the entire AAA, obtained 1 hour after contrast enhancement from 15 patients (mean age, 72.7 years +/- 8.2; range, 60-83 years), 10 men (mean age, 73.5 years +/- 7.9; range, 60-83 years) and five women (mean age, 71.2 years +/- 9.4; range 60-82), were retrospectively evaluated. Morphologic appearance and semiquantitative and contrast-to-noise ratio (CNR) analyses of the thrombi were performed. Thrombi were analyzed semiquantitatively at microscopy after staining with hematoxylin-eosin, CD68, and CD66b. Levels of promatrix metalloproteinase (pro-MMP)-2 and pro-MMP-9, MMP-2 and MMP-9, and their mRNA located in the thrombus were assessed by using zymography and quantitative reverse transcriptase polymerase chain reaction analysis. Nonparametric statistics of the Spearman rank correlation were calculated to evaluate correlations between the aneurysm thrombus signal level decrease after SPIO and the levels of CD68(+), CD66b(+) cells, pro-MMP-2 and pro-MMP-9, MMP-2 and MMP-9, and MMP-9 mRNA.The pre-SPIO CNRs in the luminal sublayer of the thrombus and the deeper thrombus were -10.20 +/- 12.69 and -5.68 +/-10.38, respectively. After SPIO, the CNRs decreased to -21.34 +/-13.07 (P.001) and -12.44 +/- 14.56, respectively (P.012). There was a significant linear correlation between the thrombus signal level decrease and the levels of CD68(+) and CD66b(+) cells, pro-MMP-9, and MMP-9 mRNA (P.05).MR imaging allows in vivo demonstration of SPIO uptake at the luminal interface of the thrombus. This uptake is correlated to the abundance of leukocytes.http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09090657/-/DC1.

Abdominal aortic aneurysm (AAA) disease is a chronic degenerative disorder and is an important cause of preventable deaths in older patients. Prevalence rates are estimated between 1.3 and 8.9% in men and between 1.0 and 2.2% in women. However, with the aging of the population and the increasing number of smokers, the incidence of the AAA is rising. The prevalence and incidence of thoracic aortic aneurysms (TAA) is more difficult to assess than for the abdominal portion of the aorta due to poorer access to screening. The overall incidence rate of TAAs is estimated at 10.4 per 100,000 person-years. The classical risk factors for atherosclerosis, such as tobacco smoking, male sex, age, hypertension, and hyperlipidemia have all been found to be also risk factors for AAA. The pathophysiology of the aorta above and below the diaphragm has shown significant differences in biomechanical properties, atherosclerotic distribution, proteolytic pattern, and cell signaling pathways that have implications in the development of an aortic aneurysm. During the last decades an overwhelming amount of evidence has been accumulated in support of genetic risk factors contributing to the development, growth and rupture of aneurysms in different segments of the arterial tree. Inflammation and matrix metalloproteinases (MMPs) also play a key role in the pathogenesis of AAA by causing proteolytic degradation of structural proteins. The size of an aneurysm is a universally recognized factor in predicting the probability of rupture; the risk of rupture increases as the diameter of the aneurysm increases. Rupture occasionally occurs in small aneurysms. The risk of rupture and dissection of TAAs also increase with increasing diameter. In addition, not only the size but also the growth rate of the aneurysm has been consistently shown to be critical in predicting rupture.

We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.

Mutations in the COL1A1 and COL1A2 genes, encoding the proα1 and 2 chains of type I collagen, cause osteogenesis imperfecta (OI) or Ehlers-Danlos syndrome (EDS) arthrochalasis type. Although the majority of missense mutations in the collagen type I triple helix affect glycine residues in the Gly-Xaa-Yaa repeat, few nonglycine substitutions have been reported. Two arginine-to-cysteine substitutions in the α1(I)-collagen chain are associated with classic EDS [R134C (p.R312C)] or autosomal dominant Caffey disease with mild EDS features [R836C (p.R1014C)]. Here we show α1(I) R-to-C substitutions in three unrelated patients who developed iliac or femoral dissection in early adulthood. In addition, manifestations of classic EDS in Patient 1 [c.1053C>T; R134C (p.R312C); X-position] or osteopenia in Patients 2 [c.1839C>T; R396C (p.R574C); Y-position] and 3 [c.3396C>T; R915C (p.R1093C); Y-position] are seen. Dermal fibroblasts from the patients produced disulfide-bonded α1(I)-dimers in ∼20% of type I collagen, which were efficiently secreted into the medium in case of the R396C and R915C substitution. Theoretical stability calculations of the collagen type I heterotrimer and thermal denaturation curves of monomeric mutant α1(I)-collagen chains showed minor destabilization of the collagen helix. However, dimers were shown to be highly unstable. The R134C and R396C caused delayed procollagen processing by N-proteinase. Ultrastructural findings showed collagen fibrils with variable diameter and irregular interfibrillar spaces, suggesting disturbed collagen fibrillogenesis. Our findings demonstrate that R-to-C substitutions in the α1(I) chain may result in a phenotype with propensity to arterial rupture in early adulthood. This broadens the phenotypic range of nonglycine substitutions in collagen type I and has important implications for genetic counseling and follow-up of patients carrying this type of mutation. Hum Mutat 28(4), 387–395, 2007. © 2007 Wiley–Liss, Inc.

The growing prevalence of valvular heart disease represents a major challenge in terms of short-term and long-term management and surveillance.1 ,2 Despite well-defined guidelines, appropriate detection and follow-up strategies are still poorly applied in valvular heart disease.3 ,4 In many countries, valvular heart diseases are managed by non-experts in the field, which may result in misdiagnosis and lead to inappropriate delays in decisions about valve interventions, and compromise patient outcome. The establishment of multidisciplinary services delivered by experts in valvular heart disease in a well-structured environment in order to provide specialised and centralised evaluation, care and education to patients with valvular heart disease has become the basis of implementation of ‘Heart Valve Centre of Excellence’ across Europe and outside Europe.5 Centres with a dedicated ‘Heart Valve Clinic’ have a designed pathway to diagnose and monitor patients with valvular heart disease. They regroup a multidisciplinary team of cardiologists, nurses, radiologists, anaesthesiologists, and surgeons proficient in diagnosing and treating all cardiac valve syndromes and disorders. This involves sophisticated cardiac valve symptoms recognition, diagnostic techniques such as three-dimensional echocardiography, cardiac magnetic resonance, cardiac CT and cardiac catheterisation.6 The ‘Heart Valve Clinic’ also provides help in optimising and monitoring medical treatment, assisting the general cardiologists for clinical decision-making, determining the correct timing and type of intervention, referring the patient to the most suitable surgeon, assessing results after intervention, and informing patients to motivate them to follow their prescribed medications and …

Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the etiology of AAAs using a genetic association study approach with human leukocyte antigen (HLA) polymorphisms (HLA-DQA1, -DQB1, -DRB1 and -DRB3-5 alleles) in 387 AAA cases and 426 controls. We observed an association with the HLA-DQA1 locus among Belgian males, and found a significant difference in the HLA-DQA1*0102 allele frequencies between AAA cases and controls. In conclusion, this study showed potential evidence that the HLA-DQA1 locus harbors a genetic risk factor for AAAs suggesting that autoimmunity plays a role in the pathogenesis of AAAs.

Background Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the etiology of AAAs using a genetic association study approach with HLA polymorphisms. Methods HLA-DQA1, -DQB1, -DRB1 and -DRB3-5 alleles were determined in 387 AAA cases (180 Belgian and 207 Canadian) and 426 controls (269 Belgian and 157 Canadian) by a PCR and single-strand oligonucleotide probe hybridization assay. Results We observed a potential association with the HLA-DQA1 locus among Belgian males (empirical p = 0.027, asymptotic p = 0.071). Specifically, there was a significant difference in the HLA-DQA1*0102 allele frequencies between AAA cases (67/322 alleles, 20.8%) and controls (44/356 alleles, 12.4%) in Belgian males (empirical p = 0.019, asymptotic p = 0.003). In haplotype analyses, marginally significant association was found between AAA and haplotype HLA-DQA1-DRB1 (p = 0.049 with global score statistics and p = 0.002 with haplotype-specific score statistics). Conclusion This study showed potential evidence that the HLA-DQA1 locus harbors a genetic risk factor for AAAs suggesting that autoimmunity plays a role in the pathogenesis of AAAs.

A 68-year-old man was hospitalized for unstable angina and underwent emergency coronary artery bypass surgery. During the operation, a pulsatile large abdominal aortic aneurysm (AAA) was discovered. To define the optimal treatment of the abdominal aneurysm, after bypass surgery, CT scans and positron emission tomography (PET) were performed, as we routinely do. PET imaging combined with immunohistologic examination showed a region of increased F-18 FDG uptake corresponding to an inflammatory infiltrate in the aortic wall in contrast to the thrombus in the aneurysm (devoid of inflammatory cells). The luminal area showed midlevel F-18 FDG uptake corresponding to circulating mediators.

Objective : Constrictive remodeling accounts for lumen loss in postangioplasty restenosis. Matrix metalloproteinase-9 (MMP-9) has been shown to prevent constrictive remodeling in vivo. To investigate potential mechanisms for this observation, we investigated the role of MMP-9 in smooth muscle cell (SMC)-mediated collagen gel contraction, an in vitro model of constrictive remodeling. Methods : Fischer rat SMCs were stably transfected with a construct-expressing rat-MMP-9 under the control of a tetracycline (Tet)-off promoter. SMCs were seeded in type I collagen gels (2.4 mg/ml) in the presence or not of tetracycline (1 μg/ml), and gel contraction was defined as the percentage of retraction of the collagen gel. The depletion of MMP-9 was obtained by using siRNA targeting MMP-9 mRNA or a blocking antibody. Results : Gel contraction was significantly reduced at all times when MMP-9 was overexpressed (Tet−) as compared with the control condition (Tet+). However, MMP-9 depletion of control (Tet+) SMCs (using siRNA or antibody) also inhibited gel contraction. To resolve the apparent discrepancy and determine if MMP-9 exerts a dose-dependent biphasic effect on gel contraction, conditioned medium and purified rat-MMP-9 were prepared. Gel contraction was significantly increased by addition of 0.8 ng/ml of MMP-9, while high concentrations of MMP-9 (≥ 100 ng/ml) inhibited contraction. The addition of BB94 and TIMP-1 did not alter the inhibitory or stimulatory effect of MMP-9. Conclusions : Our data suggest that MMP-9, independent of its proteolytic function, has a biphasic effect on SMC-mediated collagen gel contraction. Understanding the different roles of MMP-9 should allow the development of better therapeutic strategies for restenotic vascular disease.

The size of abdominal aortic aneurysms (AAA) is the most usual predictor of the risk for rupture. Because chronic metalloproteinases production and activation by inflammatory cells causes degradation of elastin and collagen in the aneurysmal wall, the detection of an increased metabolic process preceding fissuration and rupture could be a more sensitive predictor of rupture risk. We investigated the metabolic activity of the aneurysmal wall by whole-body positron emission tomography (PET) in 26 patients with a documented AAA (mean diameter 63 mm, extremes 45 mm and 78 mm). A positive (18)F-fluorodeoxyglucose ((18)F-FDG) uptake at the level of the AAA was observed in 38% of the cases (10 of 26 patients). Nine of these 10 patients required emergent or urgent aneurysmectomy for ruptured (n = 1), leaking (n = 1), rapidly expanding (n = 2), or painful (n = 5) aneurysms; the negative (18)F-FDG uptake patients had a more benign course. This preliminary study suggests a possible correlation between (18)F-FDG uptake by the aneurysm wall and the triggering of processes leading to rupture. The (18)F-FDG uptake in the aneurysm wall may correspond to the accumulation of inflammatory cells responsible for the production and activation of degrading enzymes. PET scan seems useful in high-risk patients. Positive PET imaging in these cases would help us to decide to proceed with surgery, despite factors favoring a surveillance strategy.

Cardiac resynchronization therapy (CRT) reduces functional mitral regurgitation (MR) at rest. This study assessed exercise-induced changes in MR in patients with heart failure who were helped by CRT. The determinants of these exercise-induced changes in MR were analyzed in asynchronous and resynchronized left ventricles.

Objective: This study investigated a large number of families in which at least two individuals were diagnosed with abdominal aortic aneurysms to identify the relationship of the affected relatives to the proband. Subjects and Methods: Families for the study were recruited through various vascular surgery centers in the United States, Finland, Belgium, Canada, the Netherlands, Sweden, and the United Kingdom and through our patient recruitment website (). Results: We identified 233 families with at least two individuals diagnosed with abdominal aortic aneurysms. The families originated from nine different nationalities, but all were white. There were 653 aneurysm patients in these families, with an average of 2.8 cases per family. Most of the families were small, with only two affected individuals. There were, however, six families with six, three with seven, and one with eight affected individuals. Most of the probands (82%) and the affected relatives (77%) were male, and the most common relationship to the proband was brother. Most of the families (72%) appeared to show autosomal recessive inheritance pattern, whereas in 58 families (25%), abdominal aortic aneurysms were inherited in autosomal dominant manner, and in eight families, the familial aggregation could be explained by autosomal dominant inheritance with incomplete penetrance. In the 66 families where abdominal aortic aneurysms were inherited in a dominant manner, 141 transmissions of the disease from one generation to another were identified, and the male-to-male, male-to-female, female-to-male, and female-to-female transmissions occurred in 46%, 11%, 32%, and 11%, respectively. Conclusion: Our study supports previous studies about familial aggregation of abdominal aortic aneurysms and suggests that first-degree family members, male relatives, in particular, are at increased risk. No single inheritance mode could explain the occurrence of abdominal aortic aneurysms in the 233 families studied here, suggesting that abdominal aortic aneursyms are a multifactorial disorder with multiple genetic and environmental risk factors. (J Vasc Surg 2003;37:340-5.)

Vascular injuries secondary to isolated shoulder dislocation are rare. Unawareness for closed axillary artery trauma by many physicians treating shoulder dislocations, counts often for missed or delayed diagnosis. The authors describe two cases that presented with an anterior shoulder dislocation, complicated by a disruption of the axillary artery with subsequent thrombosis. The various pathogenic mechanisms are discussed. The pathognomic triad consists of anterior shoulder dislocation, absent or diminished distal pulse and an axillary protruding hematoma. Prompt surgical arterial repair is mandatory.

Purpose: To investigate the influence of the local diameter, the intraluminal thrombus (ILT) thickness, and wall stress on the local growth rate of abdominal aortic aneurysms. Methods: The infrarenal aortas of 90 asymptomatic abdominal aortic aneurysm (AAA) patients (mean age 70 years; 77 men) were retrospectively reconstructed from at least 2 computed tomography angiography scans (median follow-up of 1 year) and biomechanically analyzed with the finite element method. Each individual AAA model was automatically sliced orthogonally to the lumen centerline and represented by 100 cross sections with corresponding diameters, ILT thicknesses, and wall stresses. The data were grouped according to these parameters for comparison of differences among the variables. Results: Diameter growth was continuously distributed over the entire aneurysm sac, reaching absolute and relative median peaks of 3.06 mm/y and 7.3%/y, respectively. The local growth rate was dependent on the local baseline diameter, the local ILT thickness, and for wall segments not covered by ILT, also on the local wall stress level (all p