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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 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

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

Growth and rupture of abdominal aortic aneurysms (AAAs) result from increased collagen turnover. Collagen turnover critically depends on specific collagenases that cleave the triple helical region of fibrillar collagen. As yet, the collagenases responsible for collagen degradation in AAAs have not been identified. Increased type I collagen degradation products confirmed collagen turnover in AAAs (median values: <1, 43, and 108 ng/mg protein in control, growing, and ruptured AAAs, respectively). mRNA and protein analysis identified neutrophil collagenase [matrix metalloproteinase (MMP)-8] and cysteine collagenases cathepsin K, L, and S as the principle collagenases in growing and ruptured AAAs. Except for modestly increased MMP-14 mRNA levels, collagenase expression was similar in growing and ruptured AAAs (anterior-lateral wall). Evaluation of posttranslational regulation of protease activity showed a threefold increase in MMP-8, a fivefold increase in cathepsins K and L, and a 30-fold increase in cathepsin S activation in growing and ruptured AAAs. The presence of the osteoclastic proton pump indicated optimal conditions for extracellular cysteine protease activity. Protease inhibitor mRNA expression was similar in AAAs and controls, but AAA protein levels of cystatin C, the principle cysteine protease inhibitor, were profoundly reduced (>80%). We found indications that this secondary deficiency relates to cystatin C degradation by (neutrophil-derived) proteases.
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PMID:Collagen degradation in the abdominal aneurysm: a conspiracy of matrix metalloproteinase and cysteine collagenases. 1732 67

Ehlers-Danlos syndrome is a connective tissue disorder caused by abnormal collagen synthesis. Vascular complications, including aneurysm formation and spontaneous arterial perforations, are difficult to manage surgically and result in significant operative mortality due to blood vessel fragility. We describe the first reported successful endovascular abdominal aortic aneurysm repair in a patient with Ehlers-Danlos syndrome. We discuss the advantages endovascular surgery offers over open surgery in these patients. We believe that endovascular repair of abdominal aortic aneurysms preferentially over open repair merits consideration in patients with Ehlers-Danlos syndrome.
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PMID:Endovascular abdominal aortic aneurysm repair in a patient with Ehlers-Danlos syndrome. 1766 11

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

Abdominal aortic aneurysm (AAA) is a common and deadly problem. The aortic diameter increases in association with a complex remodeling process that includes changes in the structure and content of key proteins, elastin and collagen. As these changes occur, the tissue mechanical properties also change. The natural history of AAA is progressive enlargement to a point of mechanical tissue failure, typically followed by death. Currently, the marker used to predict the risk of impending rupture is the largest transverse diameter. After reaching a diameter threshold of 5.5 cm, the aneurysm is surgically repaired. This criterion does not consider any patient-specific information or the known heterogeneity of the aneurysm that may, in some cases, lead to rupture before the aneurysm reaches the standard intervention threshold. Conversely, in many patients, continued observation beyond this threshold is safe. Although no medical treatment is yet approved, doxycycline has been shown to greatly reduce aortic aneurysm growth in animal models and has been shown to slow growth in several small clinical trials. Although larger prospective randomized trials are needed, one unknown is what effect doxycycline has on the structural integrity of the aortic wall. That is, does slowed aneurysm growth by doxycycline treatments, in fact, prevent rupture, or does the wall continue to weaken and the aneurysm instead ruptures at a smaller diameter? Research has begun to answer these questions before a large clinical trial begins.
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PMID:Medical therapy approach for treating abdominal aortic aneurysm. 1805 21

The novel three-dimensional (3D) mathematical model for the development of abdominal aortic aneurysm (AAA) of Watton et al. Biomech Model Mechanobiol 3(2): 98-113, (2004) describes how changes in the micro-structure of the arterial wall lead to the development of AAA, during which collagen remodels to compensate for loss of elastin. In this paper, we examine the influence of several of the model's material and remodelling parameters on growth rates of the AAA and compare with clinical data. Furthermore, we calculate the dynamic properties of the AAA at different stages in its development and examine the evolution of clinically measurable mechanical properties. The model predicts that the maximum diameter of the aneurysm increases exponentially and that the ratio of systolic to diastolic diameter decreases from 1.13 to 1.02 as the aneurysm develops; these predictions are consistent with physiological observations of Vardulaki et al. Br J Surg 85:1674-1680 (1998) and Lanne et al. Eur J Vasc Surg 6:178-184 (1992), respectively. We conclude that mathematical models of aneurysm growth have the potential to be useful, noninvasive diagnostic tools and thus merit further development.
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PMID:Evolving mechanical properties of a model of abdominal aortic aneurysm. 1805 43

We present here a coupled mathematical model of growth and failure of the abdominal aortic aneurysm (AAA). The failure portion of the model is based on the constitutive theory of softening hyperelasticity where the classical hyperelastic law is enhanced with a new constant indicating the maximum energy that an infinitesimal material volume can accumulate without failure. The new constant controls material failure and it can be interpreted as the average energy of molecular bonds from the microstructural standpoint. The constitutive model is compared to the data from uniaxial tension tests providing an excellent fit to the experiment. The AAA failure model is coupled with a phenomenological theory of soft tissue growth. The unified theory includes both momentum and mass balance laws coupled with the help of the constitutive equations. The microstructural alterations in the production of elastin and remodeling of collagen are reflected in the changing macroscopic parameters characterizing tissue stiffness, strength and density. The coupled theory is used to simulate growth and rupture of an idealized spherical AAA. The results of the simulation showing possible AAA ruptures in growth are reasonable qualitatively while the quantitative calibration of the model will require further clinical observations and in vitro tests. The presented model is the first where growth and rupture are coupled.
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PMID:A model of growth and rupture of abdominal aortic aneurysm. 1825 74


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