elastin and Aneurysm--Ruptured

Intracranial aneurysms (IAs) are thought to have a multifactorial origin. The authors undertook a comprehensive meta-analysis on all genes investigated using a case-control model in ruptured (subarachnoid hemorrhage) and unruptured aneurysms.. Electronic databases were searched until and including July 2008 for any candidate gene studied in IA or subarachnoid hemorrhage using a case-control model. The ORs and 95% CIs were determined for each gene-disease association using fixed and random effect models.. Thirty studies of 8 genes and 13 polymorphisms were analyzed among 19,961 individuals (6622 cases and 13,339 controls). Two genes and 3 polymorphisms were associated with IA. The eNOS gene T786C polymorphism (OR 1.24, 95% CI 1.0-1.54; p = 0.05) and IL-6 gene G572C polymorphism (OR 7.08, 95% CI 2.85-17.57; p < 0.0001) both showed a significant association with ruptured/unruptured IA. The IL-6/G174C polymorphism exerted a significant protective effect against IA (OR 0.49, 95% CI 0.25-0.95; p = 0.04). The other candidate genes investigated (ACE, endoglin, APOE, elastin, MMP-3, and SERPINA3) showed no significant associations.. There is a likely genetic basis to sporadic IAs. However, the evidence base is small when compared against other complex disorders.

Topics: Aneurysm, Ruptured; Antigens, CD; Apolipoproteins E; Databases, Genetic; Elastin; Endoglin; Humans; Interleukin-6; Intracranial Aneurysm; Matrix Metalloproteinase 3; Nitric Oxide Synthase Type III; Peptidyl-Dipeptidase A; Polymorphism, Single Nucleotide; Receptors, Cell Surface; Serpins; Subarachnoid Hemorrhage

Experimental aortic aneurysm may be evoked in animals by application of chemical compounds disturbing biosynthesis, posttranslating modifications and degradation of elastin and collagen, local damage of the aortic wall by chemical, thermal and mechanical factors and by increased blood pressure. Administration of protease inhibitors, anti-inflammatory drugs, agents enhancing synthesis and formation of elastic and collagen fibers and hypotensive drugs prevent formation enlargement and rupture of aneurysm.

Topics: Aneurysm, Ruptured; Animals; Aortic Aneurysm; Collagen; Disease Models, Animal; Elastin; Hemodynamics; Proline

Abdominal aortic aneurysm (AAA) is a vascular disease that results in rupture of the abdominal aorta. The risk factors for the development of AAA include smoking, male sex, hypertension, and age. AAA has a high mortality rate, but therapy for AAA is restricted to surgery in cases of large aneurysms. Clarifying the effect of dietary food on the development of AAA would be helpful for patients with AAAs. However, the relationship between dietary habits and the development of AAA is largely unknown. In our previous study, we demonstrated that adipocytes in vascular wall can induce the rupture of AAA. Therefore, we focused on the diet-induced abnormal triglyceride metabolism, which has the potential to drive AAA development. In this study, we have evaluated the effects of a high-sucrose diet on the development of AAA in a vascular hypoperfusion-induced animal model. A high sucrose diet induced high serum TG level and fatty liver. However, the AAA rupture risk and the AAA diameter were not significantly different between the control and high-sucrose groups. The intergroup differences in the elastin degradation score and collagen-positive area were insignificant. Moreover, matrix metalloproteinases, macrophages, and monocyte chemoattractant protein-1-positive areas did not differ significantly between groups. These results suggest that a high-sucrose diet does not affect the appearance of vascular adipocyte and AAA development under the vascular hypoperfusion condition.

Topics: Adipocytes; Aneurysm, Ruptured; Animals; Aortic Aneurysm, Abdominal; Collagen; Diet, Carbohydrate Loading; Dietary Sucrose; Disease Models, Animal; Elastin; Fatty Liver; Male; Rats, Sprague-Dawley; Risk Factors; Triglycerides

Pathogenesis of intracranial aneurysm is complex and the precise biomechanical processes leading to their rupture are uncertain. The goal of our study was to characterize the aneurysmal wall histologically and to correlate histological characteristics with clinical and radiological factors used to estimate the risk of rupture. A new biobank of aneurysm domes resected at the Geneva University Hospitals (Switzerland) was used. Histological analysis revealed that unruptured aneurysms have a higher smooth muscle cell (SMC) content and a lower macrophage content than ruptured domes. These differences were associated with more collagen in unruptured samples, whereas the elastin content was not affected. Collagen content and type distribution were different between thick and thin walls of unruptured aneurysms. Classification of aneurysm domes based on histological characteristics showed that unruptured samples present organized wall rich in endothelial and SMCs compared with ruptured samples. Finally, aneurysm wall composition was altered in unruptured domes of patients presenting specific clinical factors used to predict rupture such as large dome diameter, dome irregularities, and smoking. Our study shows that the wall of aneurysm suspected to be at risk for rupture undergoes structural alterations relatively well associated with clinical and radiological factors currently used to predict this risk.

Topics: Adult; Aneurysm, Ruptured; Cerebral Angiography; Collagen; Elastin; Endothelial Cells; Female; Humans; Immunohistochemistry; Intracranial Aneurysm; Macrophages; Magnetic Resonance Angiography; Male; Middle Aged; Muscle, Smooth, Vascular; Risk Factors; Smoking

Background Fragmentation of the tunica media is a hallmark of intracranial aneurysm formation, often leading to aneurysmal progression and subsequent rupture. The objective of this study is to determine the plasma level of elastin fragments in the lumen of ruptured versus unruptured human intracranial aneurysms. Methods and Results One hundred consecutive patients with/without ruptured saccular intracranial aneurysms undergoing endovascular coiling or stent-assisted coiling were recruited. Blood samples were collected from the lumen of intracranial aneurysm using a microcatheter. The tip of the microcatheter was placed inside the aneurysm's sac in close proximity to the inner wall of the dome. Plasma levels of elastin fragments were measured using an ELISA -based method. Mean plasma level of soluble human elastin fragments was significantly greater in ruptured aneurysms when compared with nonruptured aneurysms (102.0±15.5 versus 39.3±9.6 ng/mL; P<0.001). Mean plasma level of soluble human elastin fragments did not have significant correlation with age, sex, size, or aneurysm location. Conclusions The present study revealed that a significantly higher concentration of soluble human elastin fragments in the lumen of ruptured intracranial aneurysms when compared with nonruptured ones.

Topics: Adult; Aged; Aged, 80 and over; Aneurysm, Ruptured; Biomarkers; Case-Control Studies; Elastin; Endovascular Procedures; Female; Humans; Intracranial Aneurysm; Male; Middle Aged; Peptide Fragments; Young Adult

It has been suggested that the elastin gene is a candidate gene for the development of intracranial aneurysms (IAs). We investigated the association of single-nucleotide polymorphisms (SNPs) in the elastin gene in sporadic subarachnoid hemorrhage and in patients with unruptured aneurysms in China. We genotyped 446 (47.9%) IA patients (308 ruptured and 138 unruptured) and 485 (52.1%) control subjects for seven exonic and intronic SNPs in the elastin gene and then evaluated their allelic associations with sporadic ruptured and unruptured IAs. We found that IA is associated with two SNPs in the elastin gene: rs2071307 (odds ratio 2.87; 95% confidence interval, 2.26-3.64; p < 0.001) and rs2856728 (odds ratio 2.12; 95% confidence interval, 1.71-2.62; p < 0.001). Furthermore, the minor allele of rs2071307 (allele A) was also associated with IA rupture; 31.3% of patients with ruptured IAs were carriers of the minor allele, whereas only 23.2% of patients with unruptured IAs carried the minor allele (odds ratio 1.51; 95% confidence interval, 1.09-2.10; p = 0.013). In conclusion, our study indicates that the elastin gene may be associated with the formation of IAs, and importantly, that it may also be associated with the rupture of IAs.

Topics: Alleles; Aneurysm, Ruptured; Asian People; Case-Control Studies; China; Elastin; Exons; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Intracranial Aneurysm; Introns; Male; Middle Aged; Polymorphism, Single Nucleotide

MicroRNAs (miRs) regulate gene expression at the posttranscriptional level and play crucial roles in vascular integrity. As such, they may have a role in modifying abdominal aortic aneurysm (AAA) expansion, the pathophysiological mechanisms of which remain incompletely explored. Here, we investigate the role of miRs in 2 murine models of experimental AAA: the porcine pancreatic elastase (PPE) infusion model in C57BL/6 mice and the AngII infusion model in Apoe-/- mice. AAA development was accompanied by decreased aortic expression of miR-29b, along with increased expression of known miR-29b targets, Col1a1, Col3a1, Col5a1, and Eln, in both models. In vivo administration of locked nucleic acid anti-miR-29b greatly increased collagen expression, leading to an early fibrotic response in the abdominal aortic wall and resulting in a significant reduction in AAA progression over time in both models. In contrast, overexpression of miR-29b using a lentiviral vector led to augmented AAA expansion and significant increase of aortic rupture rate. Cell culture studies identified aortic fibroblasts as the likely vascular cell type mediating the profibrotic effects of miR-29b modulation. A similar pattern of reduced miR-29b expression and increased target gene expression was observed in human AAA tissue samples compared with that in organ donor controls. These data suggest that therapeutic manipulation of miR-29b and its target genes holds promise for limiting AAA disease progression and protecting from rupture.

Topics: Adolescent; Aged; Aneurysm, Ruptured; Angiotensin II; Animals; Aortic Aneurysm, Abdominal; Apolipoproteins E; Collagen; Disease Models, Animal; Disease Progression; Elastin; Gene Expression; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; MicroRNAs; Middle Aged; Pancreatic Elastase; Protein Isoforms; Swine; Young Adult

We present a 3-year-old boy with an elastin gene mutation and multiple peripheral pulmonary stenoses, who developed aneurysms of the pulmonary arteries spontaneously. We performed transcatheter occlusion of the aneurysms with detachable coils. While pulmonary arterial aneurysms may develop following pulmonary balloon angioplasty, spontaneous development is exceedingly rare. To the best of our knowledge, this is the first report describing spontaneous development of pulmonary artery aneurysms in a patient with peripheral pulmonary artery stenoses due to mutation of the elastin gene or Williams-Beuren syndrome.

Topics: Aneurysm, Ruptured; Angiography; Arterial Occlusive Diseases; Cardiac Catheterization; Child, Preschool; DNA; Elastin; Embolization, Therapeutic; Follow-Up Studies; Humans; Male; Mutation; Pulmonary Artery; Rupture, Spontaneous; Tomography, X-Ray Computed; Williams Syndrome

The occurrence of intracranial aneurysms and of aneurysmal subarachnoid hemorrhage are influenced by genetic factors. Recent genomic studies in Japan have defined 3 chromosomal loci and 1 haplotype of elastin polymorphisms as important risk factors, both for affected sib pairs and sporadic patients.. We have genotyped 2 single nucleotide polymorphisms in the elastin gene and evaluated their allelic association with intracranial aneurysm in a Central European sample of 30 familial and 175 sporadic patients and 235 population controls.. We found no allelic association between this elastin polymorphism haplotype and intracranial aneurysm.. Our data probably reflect increased genetic heterogeneity of intracranial aneurysm in Europe compared with Japan.

Topics: Adult; Age of Onset; Alleles; Aneurysm, Ruptured; Austria; Chromatography, High Pressure Liquid; DNA Mutational Analysis; Elastin; Female; Genetic Heterogeneity; Genetic Predisposition to Disease; Germany; Haplotypes; Humans; Intracranial Aneurysm; Japan; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Rupture, Spontaneous; Subarachnoid Hemorrhage

to determine whether serum elastin-derived peptides (S-EDP), are lower in patients with ruptured abdominal aortic aneurysms (rAAA) than asymptomatic (aAAA).. serum samples were collected preoperatively from 45 consecutive patients with aAAA and 15 haemodynamically stable patients with rAAA. S-EDP (ng/ml) was measured by a competitive enzyme-linked immunosorbent assay (ELISA).. S-EDP (mean +/- s.d.) was significantly lower in patients with rAAA (31.6 ng/ml +/- 6.8) than in patients with aAAA (39.4 ng/ml +/- 8.0 p=0.001).. patients with rAAA had significantly lower levels of S-EDP than patients with aAAA. The possibility that S-EDP can be used to identify patients at increased risk of rupture requires further investigation.

Topics: Aneurysm, Ruptured; Aortic Aneurysm, Abdominal; Elastin; Humans; Peptides

An in vitro model was used to determine the influence of tear depth on the propagation pressure of aortic dissections. Saline was injected into the media of segments of 20 porcine thoracic aortas to create blebs. A circumferential slit was made on the intimal side of each bleb, connecting the true lumen to the false lumen. Each aorta was then pressurized under no-flow conditions until propagation in either the anterograde or retrograde direction occurred. Histological sections of each principal propagating edge were used to determine depth of tear, measured as the ratio of elastin layers in the intimal flap to the elastin layers in the intact wall. Propagation occurred for tear depths ranging from 0.44 to 0.89, with dissections closest to the adventitia (with tear depths near 1) requiring the lowest pressures. Propagation pressure (P) depends on the number of elastin layers (L) in the outer wall of a dissection, P = 0.44 L + 25(kPa), r2 = 0.465, p = 0.003 and also on tear depth (d): P = -58 d + 81(kPa), r2 = 0.547, p < 0.001. Various in vivo factors are discussed which may affect these experimentally determined relationships.

Topics: Algorithms; Aneurysm, Ruptured; Animals; Aortic Aneurysm, Thoracic; Aortic Dissection; Blood Pressure; Elastic Tissue; Elastin; Models, Cardiovascular; Pressure; Stress, Mechanical; Swine; Tunica Intima

alpha 1-Antitrypsin (AAT) and alpha 2-macroglobulin (AMG) are elastase inhibitors that bind the enzyme and reduce measured levels of free elastase. It was recently demonstrated that some patients with intracranial aneurysms have significantly elevated plasma elastase (PE) levels. Although this elevation is unrelated to plasma AAT, it is unknown whether abnormal AAT phenotypes or reduced AMG levels play a role. Moreover, the pathological significance of this elevation is not understood.. Plasma from 24 patients with aneurysms (ruptured, n = 15; unruptured, n = 9) and 10 age-matched patients who comprised a control group was analyzed for PE and AMG levels by enzyme-linked immunosorbent assay and for AAT phenotype by isoelectric focusing. Sections of superficial temporal temporal artery obtained from these patients at the time of surgery were examined for evidence of elastin degradation by using a van Gieson stain, with scoring on a nine-point quantitative scale.. Patients with aneurysms showed significantly elevated PE levels (119 +/- 28 versus 17 +/- 7 micrograms/ml, P < 0.05), but AMG levels were not decreased. AAT phenotypic abnormalities were observed in 10% (2 of 20) of the patients with aneurysms, but this was not different from the expected population incidence (7%). Elastin degradation scores were significantly higher in patients with aneurysms than in patients control group (4.26 +/- 0.54 versus 1.21 +/- 0.43, P < 0.05). In addition, patients with higher elastase levels (> 80 micrograms/ml) demonstrated 55% higher degradation scores than did those with lower elastase levels (< 80 micrograms/ml).. These data suggest that high PE levels may play a role in systemic arterial elastin degradation seen in patients with intracranial aneurysms. These data also support the contention that elevated elastase levels are not the result of decreased protease inhibitor levels. Although PE levels were significantly higher for the entire group of patients with aneurysms, this assay has relatively low sensitivity for predicting the presence of unruptured aneurysms. Additional study is necessary to determine whether serum elastase levels greater than 80 micrograms/ml, in the setting of other risk factors, are useful in identifying asymptomatic patients for additional screening.

Topics: Adult; Aged; alpha 1-Antitrypsin; alpha-Macroglobulins; Aneurysm, Ruptured; Craniotomy; Elastic Tissue; Elastin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intracranial Aneurysm; Male; Middle Aged; Pancreatic Elastase; Predictive Value of Tests; Prospective Studies; Reference Values; Subarachnoid Hemorrhage; Temporal Arteries

Aneurysms are morphologically classified as true or false based on the nature of their walls. True aneurysms are composed of all or parts of layers of the vessel. False aneurysms are the result of rupture and their walls have only fibrous tissues. The orifice of false aneurysms is narrow relative to the aneurysmal diameter and thus they are grossly or angiographically referred to as punched-out lesions. Hence false aneurysms present with punched-out lesions, but in reverse, are all of punched-out lesions false aneurysms? We experienced some cases of punched-out lesions which histologically contained traces of elastin, and the purpose of this report was to histologically investigate grossly punched-out lesions. We examined 671 elderly autopsy cases, and a total of 21 grossly punched-out lesions in the aorto-iliac region were selected. They were histologically classified as false, "pseudo-false", or "disguised" aneurysm. False aneurysms were found in 3 patients (0.45%), and were histologically mycotic. A total of 5 "pseudo-false" aneurysms were found in 3 patients (0.45%). They histologically contained traces of elastin, and thus they were categorised in true aneurysms. A total of 13 "disguised" aneurysms were found in 6 patients (0.89%). They were true fusiform aneurysms with an eccentric thrombus, on which a fibrin-cap formed a narrow orifice. Partial sections are insufficient for diagnosis; cross-sections are necessary. To the best of our knowledge, there have been no reports of "pseudo-false" or "disguised" aneurysms in the aorto-iliac region.

Topics: Aged; Aged, 80 and over; Aneurysm, False; Aneurysm, Infected; Aneurysm, Ruptured; Aortic Aneurysm, Abdominal; Elastin; Female; Humans; Iliac Aneurysm; Immunohistochemistry; Male; Retrospective Studies; Rupture, Spontaneous

Laplace's law, which describes a linear relation between the tension and the radius, is often used to characterize the mechanical response of the aneurysm wall to distending pressures. However, histopathological studies have confirmed that the wall of the fully developed aneurysm consists primarily of collagen and is subject to large increases in tension for small increases in the radius, i.e., a nonlinear relationship exists between the tension within the aneurysm wall and the radius. Thus, a nonlinear version of Laplace's law is proposed to accurately describe the development and rupture of a fusiform saccular aneurysm. The fusiform aneurysm was modelled as a thin-walled ellipsoidal shell with a major axis radius, Ra, minor axis radius, Rb, circumferential tension, S0, and meridional tension, S phi, with phi defining the angle from the surface normal. Using both linear and nonlinear models, differential expressions of the volume distensibility evaluated at 90 degrees were used to determine the critical radius of the aneurysm along the minor axis from S0 and S phi in terms of the following geometric and biophysical variables; A, elastic modulus of collagen; E, elastic modulus of the aneurysm (elastin and collagen); t, wall thickness; P, systolic pressure; and Ra. For typical physiological values of A = 2.8 MPa, E = 1.0 MPa, T = 40 microns, P = 150 mmHg, and Ra = 4Rb, the linear model yielded critical radii of 4.0 mm from S phi and 2.2 mm from S0. The resultant critical radius was 4.56 mm. Using the same values, the critical radii from the tension components of the nonlinear model were 3.5 mm from S phi and 1.9 mm from S0.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aneurysm, Ruptured; Cerebral Arteries; Collagen; Elasticity; Elastin; Humans; Intracranial Aneurysm; Models, Theoretical