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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abdominal aorta aneurysms are quite common in elderly people, coexisting frequently with manifestations of atherosclerotic degenerative disease and in patients with already known risk factors such as hypertension, hyperlipidemia or tobacco habits. According to the most recent pathogenic concepts, the disease is caused by the inflammation of the arterial wall, leading to the destruction of elastin, and apoptosis of the smooth muscle cells of the media, associated to biomechanical factors, rendering the aortic cylinder into a sphere, with progressive expansion, coursing with growing risks of rupture, often fatal. The enormous progress noticed in the field of cellular and molecular biology and a better understanding of the intimal mechanisms involved in the pathogenesis of the disease, together with the new achievements occurred in pharmacotherapy and genetic therapy, will be able to offer in the near future, the creation of new alternatives for the medical management of this entity, preventing and controlling its progressive and expansive nature, as well as the severe and even lethal complications that can cause. In this paper the author makes an update on the new etiopathogenic concepts and new therapeutic modalities that have been tested in the medical management of the abdominal aortic aneurysm.
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PMID:[Pathogenesis and medical treatment of the abdominal aortic aneurysm: an update]. 1705 30

Abdominal aortic aneurysm (AAA) is a common disease that, when surgical treatment is inapplicable, results in rupture of the aorta with high mortality. Although nonsurgical treatment for AAA is eagerly awaited, the destruction of the aortic walls in AAA has been considered an irreversible process. We found that c-Jun N-terminal kinase (JNK) is highly activated in human AAA walls. We also found that JNK activity is essential for the expression of matrix metalloproteinase (MMP)-9 and, concurrently, suppression of the extracellular matrix (ECM) biosynthesis. We therefore investigated the role of JNK in the pathogenesis of AAA in vivo. We created a mouse AAA model by periaortic application of CaCl(2), which was accompanied by activation of JNK and MMPs, and suppression of lysyl oxidase (LOX), which is an essential biosynthetic enzyme for collagen and elastin fibers. Our data indicate that, in addition to MMP activities, suppression of ECM biosynthesis may contribute to the AAA pathogenesis because local LOX gene delivery prevented AAA formation. Treatment of mice with SP600125, a specific JNK inhibitor, completely abrogated the formation of CaCl(2)-induced AAA. Furthermore, SP600125 treatment after the establishment of AAA caused a reduction in the aortic diameters with normalized tissue architecture. SP600125 treatment also caused significant regression of angiotensin II-induced AAA in ApoE-null mice after its establishment, as demonstrated by serial ultrasonographic studies in live animals. These data demonstrate that JNK dictates the abnormal ECM metabolism in AAA pathogenesis by enhancing tissue degradation and suppressing tissue repair. Therefore, inhibition of JNK may provide a novel therapeutic option for AAA.
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PMID:Regression of abdominal aortic aneurysm by inhibition of c-Jun N-terminal kinase in mice. 1718 24

The role of matrix metalloproteinases (MMPs) in the pathogenesis of abdominal aortic aneurysm (AAA) has focused on the degradation of the extracellular matrix (ECM). The new frontier of MMP biology involves the role of MMPs in releasing cryptic fragments and neoepitopes from the ECM and the impact of MMPs on the regulation of the inflammatory response. The ECM is a complex structure, much more important than an inert scaffold. Both MMP-2 and MMP-9 expose a cryptic epitope that controls angiogenesis. MMPs inhibit angiogenesis through the release of endostatin, endorepellin, arresten, canstatin, and tumstatin. Other breakdown products of the ECM include fragments of fragmin and elastin degradation products (EDPs). In addition, the ECM contains embedded vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-beta). Inflammation is a complex, highly regulated system that involves the identification of injury or infection, response to the injury or infection, repair and healing, and return to normal homeostasis. In some instances, the inflammatory process leads to a pathologic process that is damaging to the host. MMPs play an important role in the control of the inflammatory response through the modification of proinflammatory cytokines, chemokines, and shedding of membrane receptors. Genetic association studies have been performed to help determine the genetic risk associated with certain single nucleotide polymorphisms (SNPs) However, because of the variability in the patient populations and the size of the population, it is difficult to draw any conclusions from these studies. While the etiology of AAA remains unknown, understanding of the inflammatory process and its regulatory points will develop new strategies for the treatment of AAA. Perhaps one difficulty with understanding the pathogenesis of AAA is the lack of precise definition of the phenotype.
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PMID:Abdominal aortic aneurysm as a complex multifactorial disease: interactions of polymorphisms of inflammatory genes, features of autoimmunity, and current status of MMPs. 1718 28

Most abdominal aortic aneurysms (AAAs) with a diameter indicating need for surgical repair contain intraluminal thrombus (ILT). The development of AAA is linked to degradation of elastin and collagen. These changes are more pronounced in the aneurysm wall covered by the ILT, which also shows more signs of inflammation and is thinner compared to the aneurysm wall exposed to flowing blood. The rate of increase in diameter of AAA correlates with increased thrombus growth and rupture. CT examinations of patients with rupture have demonstrated contrast appearing in the thrombus suggesting bleeding into it. Studies using gene array of human aneurysm specimens have shown that most matrix metalloproteinases (MMP) were upregulated in the thrombus-free wall. Analyses by zymography, however, demonstrate gelatinase activity in the interface between the thrombus and the underlying wall and in the media of the wall not covered by a thrombus. The thrombus contains large amounts of neutrophils. Neutrophil gelatinase associated lipocalin (NGAL) is involved in the regulation of MMP-9 activity and prevents its inactivation, thus augmenting the proteolytic effect. It has been identified in all layers of the ILT. The presence of NGAL/MMP-9 complexes throughout the thrombus and in the thrombus-covered wall may contribute to the increased proteolytic degradation seen in this wall segment. In conclusion, the presence, growth, and thickness of the ILT have been shown to be associated with growth and risk of rupture. The wall underlying the thrombus is thinner and shows more signs of proteolytic degradation. Increased proteolytic activity by MMP-9 may be mediated by binding to NGAL.
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PMID:The intraluminal thrombus as a source of proteolytic activity. 1718 29

The relative importance of collagen and elastin in formation, expansion, and rupture of abdominal aortic aneurysms (AAAs) has been investigated extensively. Aortic compliance, which is a relevant component of cardiac afterload, is also determined by the relative amount of media proteins in large arteries as well as by pathological arterial processes. The objective of this study was to determine if thoracic aortic compliance was different in patients with ruptured AAAs compared to those undergoing elective AAA repair. The study was carried out in 43 patients with infrarenal AAAs in the postoperative period. The first group (A) included 17 patients undergoing emergency ruptured AAA repair. The second group (B) included 26 patients operated on for an AAA who underwent elective repair. Patients were studied by a noninvasive Doppler echocardiography. Pulse wave velocity (PWV) was determined in the descending thoracic aorta. Results show that patients with electively repaired AAAs had an accelerated pulse wave transmission, typical of an atherosclerotic aorta with a Gaussian distribution (PWV 9.26 m/sec +/- 1.27). In contrast, patients with ruptured aneurysms presented in a distribution with three peaks. A striking increase in aortic compliance (41% of patients with PWV<6 m/sec in group A vs. 3% of group B) was observed in patients with ruptured AAAs.
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PMID:Thoracic aortic compliance as a determinant of rupture of abdominal aortic aneurysms. 1718 57

The abdominal aortic aneurysm is a dilatation of infrarenal part of aorta. Its ethiology is still unknown. An infection and congenital disorders of conjunctive tissue are regarded as the main risc factors. Other factors could be a perimural thrombus and elastin and colagen degradation. It's not proved that atheromatosis is a risc factor. The disease concerns mainly the old males. Not treated aneurysm grows until rupture. The aneurysms are usually asympthomatic. Majority of them are found incidentally. Ultrasonography and computed tomography are used to extended diagnosis. The open surgery or endovascular surgery are only possible ways of treatment. The aneurysm with diameter over 55 milimeters, sympthomatic or rupted is an indication for surgery. The aim of the open surgery is implantation of the vascular prosthesis into retroperitoneal space. Endovascular method consist in placement of stent-graft in the lumen of aneurysm through small incision in a peripherial vessel. Stent-graft consists of metal chassis covered by classic vascular prosthesis. This method still requires the long-term assessment.
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PMID:[The treatment of abdominal aortic aneurysms by use of endovascular prosthesis and classic vascular prosthesis]. 1719 Feb 89

Several case-control studies have shown a significant negative association between diabetes and abdominal aortic aneurysm (AAA). This interaction has the potential to further our understanding of these two diseases but has attracted little research. The changes seen in the walls of aneurysmal aortas include inflammation and the activation of proteolytic pathways resulting in loss of elastin and other structural proteins. In contrast, diabetes is associated with increased synthesis and reduced degradation of matrix. The deposition of advanced glycation end products also renders vascular matrix resistant to proteolysis in diabetic patients. The aim of our present minireview is to compare the changes in matrix biology seen in diabetes and AAA and to explore molecular mechanisms that may explain the negative association and identify possible therapeutic implications.
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PMID:Matrix biology of abdominal aortic aneurysms in diabetes: mechanisms underlying the negative association. 1752 95

It has been suggested that the intraluminal thrombus of abdominal aortic aneurysms (AAAs) predisposes for AAA enlargement and rupture. The growth of the AAA is dependent on proteolytic degradation of elastin. Here, we analysed whether the neutrophil gelatinase-associated lipocalin (NGAL) is expressed within the thrombus and the aneurysm wall. NGAL can bind to metalloproteinase-9 (MMP-9) and inhibit its degradation, thereby preserving enzymatic activity. Biopsies were obtained from thrombus-free and thrombus-covered aneurysm wall and the intraluminal thrombus from patients undergoing elective surgery for AAA. Immunohistochemistry and real-time PCR were used to study NGAL and MMP-9 expression. Immunoprecipitation, gel zymography, Western blot and ELISA were used to detect and quantify NGAL/MMP-9 complexes. NGAL was detected in the thrombus, the interface between the thrombus and the underlying wall and in the wall itself. Double staining showed that neutrophils are the major source of NGAL expression. Immunoprecipitation of MMP-9 with antibody against NGAL showed that complexes of NGAL and active MMP-9 were present in thrombus, the interface fluid and the aneurysm wall. Western blot analyses using non-reducing conditions and gel zymography demonstrated that high-molecular-weight complexes of NGAL/MMP-9 were present within the different regions. The concentration of the NGAL/MMP-9 complex was highest in the luminal part of the thrombus. In conclusion, NGAL in complex with activated MMP-9 is present in AAA wall and thrombus. Neutrophil-derived NGAL could enhance the proteolytic activity associated with AAA, but the importance of this mechanism for aneurysm growth remains to be shown.
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PMID:Presence of NGAL/MMP-9 complexes in human abdominal aortic aneurysms. 1772 27

Because current therapy to treat abdominal aortic aneurysm (AAA), and particularly to manage small AAA, is limited to elective surgical repair, we explored less invasive molecular therapy by simultaneous inhibition of the transcription factors nuclear factor (NF)kappaB and ets using a decoy strategy. Both NFkappaB and ets were shown to be markedly activated in human AAA. In addition, NFkappaB- and ets-positive cells were increased in the aneurysm wall, and a part of the expression of NFkappaB and ets was detected in migrating macrophages. Thus, we used chimeric decoy oligodeoxynucleotides (ODNs) containing consensus sequences of both NFkappaB and ets binding sites to treat AAA. Inhibitory effects of chimeric decoy ODNs on matrix metalloproteinase-1 and -9 expression were confirmed by ex vivo experiments using a human aorta organ culture. To examine the regressive effect in a rabbit already-formed AAA model, transfection by wrapping a delivery sheet containing chimeric decoy ODNs around the aneurysm was performed 1 week after incubation with elastase. Importantly, treatment with chimeric decoy ODNs significantly decreased the size of AAA. Interestingly, significant preservation of elastic fibers was observed with chimeric decoy ODN treatment, accompanied by a reduction of matrix metalloproteinase-2 and -9 and induction of macrophage apoptosis. Regression of AAA was also associated with an increase in elastin and collagen type I and III synthesis in the aneurysm wall. Minimally invasive molecular therapy targeted to the inhibition of NFkappaB and ets is expected to be useful for AAA through the rebalance of matrix synthesis and degradation.
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PMID:Regression of abdominal aortic aneurysms by simultaneous inhibition of nuclear factor kappaB and ets in a rabbit model. 1788 20

The incidence of and mortality from ruptured infrarenal abdominal aortic aneurysm (AAA) are increasing. Therefore, it is important to identify groups at high risk. Tobacco use, hypertension, a family history of AAA, and male sex are clinical risk factors for the development of an aneurysm. Chronic inflammation and enzymatic degradation of elastin and collagen constitute the prominent pathogenetic mechanism of infrarenal AAA. Intervals for surveillance depend on the aneurysm diameter, taking into account that AAA >5.5 cm should be referred to a vascular surgeon. Asymptomatic patients with an infrarenal AAA should be medically optimized before repair. Symptomatic aneurysms present with back, abdominal, or leg pain and require urgent surgical attention. Rupture of an AAA involves complete loss of aortic wall integrity and is a surgical emergency requiring immediate repair.
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PMID:[Infrarenal abdominal aortic aneurysms]. 1797 23


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