Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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 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.
 ...
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.
 ...
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.
 ...
PMID:A model of growth and rupture of abdominal aortic aneurysm. 1825 74

Abdominal aortic aneurysm (AAA) is histologically characterized by medial degeneration and various degrees of chronic adventitial inflammation, although the mechanisms for progression of aneurysm are poorly understood. In the present study, we carried out histological study of AAA tissues of patients, and interventional animal and cell culture experiments to investigate a role of mast cells in the pathogenesis of AAA. The number of mast cells was found to increase in the outer media or adventitia of human AAA, showing a positive correlation between the cell number and the AAA diameter. Aneurysmal dilatation of the aorta was seen in the control (+/+) rats following periaortic application of calcium chloride (CaCl2) treatment but not in the mast cell-deficient mutant Ws/Ws rats. The AAA formation was accompanied by accumulation of mast cells, T lymphocytes and by activated matrix metalloproteinase 9, reduced elastin levels and augmented angiogenesis in the aortic tissue, but these changes were much less in the Ws/Ws rats than in the controls. Similarly, mast cells were accumulated and activated at the adventitia of aneurysmal aorta in the apolipoprotein E-deficient mice. The pharmacological intervention with the tranilast, an inhibitor of mast cell degranulation, attenuated AAA development in these rodent models. In the cell culture experiment, a mast cell directly augmented matrix metalloproteinase 9 activity produced by the monocyte/macrophage. Collectively, these data suggest that adventitial mast cells play a critical role in the progression of AAA.
 ...
PMID:Adventitial mast cells contribute to pathogenesis in the progression of abdominal aortic aneurysm. 1845 39

Recently, atherosclerosis has been considered to be the result of inflammation. Interestingly, hydroxymethylglutaryl-coenzyme (HMG-Co) A inhibitors (statins), which are clinically used as lipid-lowering agents, have been reported to have various anti-inflammatory effects. As abdominal aortic aneurysm (AAA) is a common degenerative condition associated with atherosclerosis, this study was designed to investigate the inhibitory effect of a statin, atorvastatin, on aneurysm formation apart from its lipid-lowering effect. We employed an elastase-induced rat AAA model, as statins do not lower cholesterol in rats. Mean aneurysm diameter was significantly smaller in the atorvastatin treatment group as compared to control at 4 weeks after surgery (P<0.05). Interestingly, atorvastatin inhibited the expression of ICAM and MCP-1, followed by the suppression of macrophage recruitment into the aortic wall at 1 week after operation. A significant reduction in MMP-12, but not MMP-2, -3 and -9, expression was also observed by treatment with atorvastatin at 1 week after surgery. In addition, synthesis of collagen and elastin in the vascular wall were significantly increased by atorvastatin. Here, the present study demonstrated a direct effect of atorvastatin to inhibit the progression of aortic aneurysm, independent of its lipid-lowering effect. This study suggests new therapeutic aspects of statins to inhibit the progression of aneurysms.
 ...
PMID:Inhibition of development of experimental aortic abdominal aneurysm in rat model by atorvastatin through inhibition of macrophage migration. 1848 27

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 AAA needs to be surgically repaired. This criterion does not consider any patient-specific information or heterogeneity of the AAA that may, in some cases, lead to rupture before the AAA reaches the standard intervention threshold. Conversely, in many patients, continued observation beyond this threshold is safe. While no medical treatment is yet approved, doxycycline (Doxy) has been shown to greatly reduce AAA growth in animal models and has been shown to slow growth in 1 small clinical trial. While larger prospective randomized trials are needed, one unknown is what effect Doxy has on the structural integrity of the aortic wall. That is, does slowed AAA growth, by Doxy treatment, prevent rupture, or does the wall continue to weaken and the AAA instead ruptures at a smaller diameter? Using an established animal model of AAA, we begun to determine the changes in tissue mechanics compliance of the aorta as the AAA develops. Our current research is focused on verifying that these changes mimic the observed changes seen in the human population as reported by other researchers, so that we can confidently study how potential drug therapies may affect wall strength and compliance in the human population. The long-term objectives are to understand better factors related to progression of AAA and help verify that drug therapy with Doxy will decrease the chance of rupture by preventing wall weakening and maintaining function of the aorta.
 ...
PMID:Screening aortic drug treatments through arterial compliance measurements. 1885 13

During arterial aneurysm formation, levels of the membrane-anchored matrix metalloproteinase, MT1-MMP, are elevated dramatically. Although MT1-MMP is expressed predominately by infiltrating macrophages, the roles played by the proteinase in abdominal aortic aneurysm (AAA) formation in vivo remain undefined. Using a newly developed chimeric mouse model of AAA, we now demonstrate that macrophage-derived MT1-MMP plays a dominant role in disease progression. In wild-type mice transplanted with MT1-MMP-null marrow, aneurysm formation induced by the application of CaCl2 to the aortic surface was almost completely ablated. Macrophage infiltration into the aortic media was unaffected by MT1-MMP deletion, and AAA formation could be reconstituted when MT1-MMP+/+ macrophages, but not MT1-MMP+/+ lymphocytes, were infused into MT1-MMP-null marrow recipients. In vitro studies using macrophages isolated from either WT/MT1-MMP-/- chimeric mice, MMP-2-null mice, or MMP-9-null mice demonstrate that MT1-MMP alone plays a dominant role in macrophage-mediated elastolysis. These studies demonstrate that destruction of the elastin fiber network during AAA formation is dependent on macrophage-derived MT1-MMP, which unexpectedly serves as a direct-acting regulator of macrophage proteolytic activity.
 ...
PMID:Membrane-type 1 matrix metalloproteinase regulates macrophage-dependent elastolytic activity and aneurysm formation in vivo. 1901 Jul 78

The association between an abdominal aortic aneurysm (AAA) and tuberous sclerosis (TS) is rare. An 8-month-old girl presented with a seizure, and the clinical evaluation revealed TS. An abdominal evaluation showed a 3-cm infrarenal AAA. A normal diameter of infrarenal aorta for an 8-month-old girl is about 6mm. The patient underwent an open repair with a polytetrafluoroethylene (PTFE) prosthesis. The pathology showed a loss of elastin fibres in the media of the aorta. The graft was patent on computed tomography (CT) angiography, performed 4 months after the operation. However, the patient died of complications related to seizures 5 years after the surgery. The graft remained patent until the time of death.
 ...
PMID:An abdominal aortic aneurysm in an 8-month-old girl with tuberous sclerosis. 1923 Dec 54

Abdominal aortic aneurysms (AAAs) comprise the tenth leading cause of death in Caucasian males 65 to 74 years of age and accounted for nearly 16,000 deaths overall in 2000. Therefore, understanding the pathophysiology of AAAs is an important undertaking. Clinically, multiple risk factors are associated with the development of AAAs, including increasing age, positive smoking history, and hypertension. Male gender is also a well-established risk factor for the development of an AAA, with a 4:1 male to female ratio. The reason for this gender disparity is unknown. The pathogenesis of AAAs formation is complex and multifactorial. Histologically, AAAs are characterized by early chemokine-driven leukocyte infiltration into the aortic wall. Subsequent destruction of elastin and collagen in the media and adventitia ensues owing to excessive local production of matrix-degrading enzymes and is accompanied by smooth muscle cell loss and thinning of the aortic wall. At present, no medical therapies are available to treat patients with aortic aneurysms, using only the crude measurement of aortic diameter as a threshold for which patients must undergo life-threatening and costly surgery. Defining the early mechanisms underlying gender-related differences in AAA formation is critical as understanding differences in disease patterns based on gender may allow us to develop new translational approaches to the prevention and treatment of patients with aortic aneurysms.
 ...
PMID:Gender differences in abdominal aortic aneurysms. 1942 7

Abdominal aortic aneurysm (AAA) is an important health problem. Elective surgical treatment is recommended on the basis of an individual's risk of rupture, which is predicted by AAA diameter. However, the natural history of AAA differs between patients and a reliable and individual predictor of AAA progression (growth and expansion rates) has not been established. Several circulating biomarkers are candidates for an AAA diagnostic tool. However, they have yet to meet the triad of biomarker criteria: biological plausibility, correlation with AAA progression, and prediction of treatment effect on disease outcome. Circulating levels of markers of extracellular matrix degeneration, such as elastin peptides, aminoterminal propeptide of type III procollagen, elastase-alpha1-antitrypsin complexes, matrix metalloproteinase 9, cystatin C, plasmin-antiplasmin complexes and tissue plasminogen activator, have been correlated with AAA progression and have biological plausibility. Although studies of these markers have shown promising results, they have not yet led to a clinically applicable biomarker. In future studies, adjustment for initial AAA size, smoking history and the measurement error for determination of AAA size, among other variables, should be taken into account. A large, prospective, standardized, follow-up study will be needed to investigate multiple circulating biomarkers for their potential role in the prediction of AAA progression, followed by a study to investigate the effect of treatment on the circulating levels of biomarkers.
 ...
PMID:Biomarkers of AAA progression. Part 1: extracellular matrix degeneration. 1946 92


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>