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

Biomechanical studies suggest that one determinant of abdominal aortic aneurysm (AAA) rupture is related to the stress in the wall. In this regard, a reliable and accurate stress analysis of an in vivo AAA requires a suitable 3D constitutive model. To date, stress analysis conducted on AAA is mainly driven by isotropic tissue models. However, recent biaxial tensile tests performed on AAA tissue samples demonstrate the anisotropic nature of this tissue. The purpose of this work is to study the influence of geometry and material anisotropy on the magnitude and distribution of the peak wall stress in AAAs. Three-dimensional computer models of symmetric and asymmetric AAAs were generated in which the maximum diameter and length of the aneurysm were individually controlled. A five parameter exponential type structural strain-energy function was used to model the anisotropic behavior of the AAA tissue. The anisotropy is determined by the orientation of the collagen fibers (one parameter of the model). The results suggest that shorter aneurysms are more critical when asymmetries are present. They show a strong influence of the material anisotropy on the magnitude and distribution of the peak stress. Results confirm that the relative aneurysm length and the degree of aneurysmal asymmetry should be considered in a rupture risk decision criterion for AAAs.
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PMID:Mechanical stresses in abdominal aortic aneurysms: influence of diameter, asymmetry, and material anisotropy. 1841 10

Collagen type I is an AAB heterotrimer assembled from two alpha1 chains and one alpha2 chain. Missense mutations in either of these chains that substitute a glycine residue in the ubiquitous X-Y-Gly repeat with a bulky amino acid leads to osteogenesis imperfecta (OI) of varying severity. These mutations have been studied in the past using collagen-like peptide homotrimers as a model system. However, homotrimers, which by definition will contain glycine mutations in all the three chains, do not accurately mimic the mutations in their native form and result in an exaggerated effect on stability and folding. In this article, we report the design of a novel model system based upon collagen-like heterotrimers that can mimic the glycine mutations present in either the alpha1 or alpha2 chains of type I collagen. This design utilizes an electrostatic recognition motif in three chains that can force the interaction of any three peptides, including AAA (all same), AAB (two same and one different), or ABC (all different) triple helices. Therefore, the component peptides can be designed in such a way that glycine mutations are present in zero, one, two, or all three chains of the triple helix. With this design, we for the first time report collagen mutants containing one or two glycine substitutions with structures relevant to native forms of OI. Furthermore, we demonstrate the difference in thermal stability and refolding half-life times between triple helices that vary only in the frequency of glycine mutations at a particular position.
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PMID:Synthetic collagen heterotrimers: structural mimics of wild-type and mutant collagen type I. 1848 52

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.
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PMID:Inhibition of development of experimental aortic abdominal aneurysm in rat model by atorvastatin through inhibition of macrophage migration. 1848 27

BMP2 signaling and RUNX2 regulatory pathways converge for transcriptional control of bone formation in vivo. SMAD proteins are recruited to RUNX2 regulatory complexes via an overlapping nuclear matrix targeting signal/Smad interacting domain sequence (391-432) in Runx2. To establish the contribution of RUNX2-SMAD interaction to osteoblastogenesis, we characterized a number of point mutants. Only a triple mutation of amino acids 426-428 (HTY-AAA) results in loss of RUNX2 interactions with either BMP2- or TGF-beta- responsive SMADs and fails to integrate the BMP2/TGF-beta signal on target gene promoters. In a Runx2 null cell reconstitution assay, the HTY mutant did not activate the program of osteoblast differentiation (alkaline phosphatase, collagen type 1, osteopontin, bone sialoprotein and osteocalcin) in response to BMP2 signaling. Thus, subnuclear targeting function and formation of a RUNX2-SMAD osteogenic complex are functionally inseparable. Taken together, these studies provide direct evidence that RUNX2 is essential for execution and completion of BMP2 signaling for osteoblast differentiation.
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PMID:Specific residues of RUNX2 are obligatory for formation of BMP2-induced RUNX2-SMAD complex to promote osteoblast differentiation. 1872 44

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.
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PMID:Screening aortic drug treatments through arterial compliance measurements. 1885 13

Clinical evidence links increased aortic collagen content and stiffness to abdominal aortic aneurysm (AAA) formation. However, the possibility that excess collagen contributes to AAA formation remains untested. We investigated the hypothesis that augmented collagen promotes AAA formation, and employed apoE-null mice expressing collagenase-resistant mutant collagen (Col(R/R)/apoE(-/-)), heterozygote (Col(R/+)/apoE(-/-)), or wild-type collagen (Col(+/+)/apoE(-/-)) infused with angiotensin II to induce AAA. As expected, the aortas of Col(R/R)/apoE(-/-) mice contained more interstitial collagen than those from the other groups. Angiotensin II treatment elicited more AAA formation in Col(R/R)/apoE(-/-) mice than Col(R/+)/apoE(-/-) or Col(+/+)/apoE(-/-) mice. Aortic circumferences correlated positively with collagen content, determined by picrosirius red and Masson trichrome staining. Mechanical testing of aortas of Col(R/R)/apoE(-/-) mice showed increased stiffness and susceptibility to mechanical failure compared to those of Col(+/+)/apoE(-/-) mice. Optical analysis further indicated altered collagen fiber orientation in the adventitia of Col(R/R)/apoE(-/-) mice. These results demonstrate that collagen content regulates aortic biomechanical properties and influences AAA formation.
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PMID:Genetically engineered resistance for MMP collagenases promotes abdominal aortic aneurysm formation in mice infused with angiotensin II. 1915 55

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.
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PMID:Gender differences in abdominal aortic aneurysms. 1942 7

The objective of this work was to assess whether selective proteolysis of elastin and/or collagen in a porcine aorta followed by mechanical creep loading would result in an aneurysm-like permanent tissue stretch. The underlying motivations were to (1) test the feasibility of developing an in vitro abdominal aortic aneurysm (AAA) model, and (2) understand what role, if any, that passive creep-induced stretching plays in aneurysmal dilation. Multiple circumferentially oriented flat specimen strips were cut from the porcine thoracic aorta of ten adult pigs. Specimens were subjected to one of six treatment protocols: Untreated controls (UC;N=23), complete elastin degradation (E;N=10), partial elastin degradation (E(p);N=10), partial collagen degradation (C(p);N=22), and partial degradation of both elastin and collagen (E(p)+C(p);N=3). All specimens were then subjected to cyclic creep (10 min/cycle) with increasing load amplitude until failure. The zero-load strain prior to the creep cycle where failure occurred was defined as load-induced plastic strain. The plastic strain induced by treatment alone, creep loading alone and the total was determined for all specimens. The total plastic strain was significantly greater for E (mean +/- SD = 48.2 +/-17.6,p<0.005), E(p)(41.6+/-11.1,p<0.0005), but not for E(p)+C(p)(48.9+/-21.6,p=0.17) and C(p)(22.2+/-12.8,p=0.14) compared to UC (17.7+/-6.1). Of the total plastic strain, treatment-induced plastic strain was high for those specimens subjected to partial or total elastin degradation (E,E(p),E(p)+C(p)), but not for those where elastin was intact (C(p)). However, load-induced plastic strain in the treated specimens was not different in any of the treated groups compared to controls. Maximum total plastic strain of 78.6% was induced in one porcine aortic tissue from the E group. Even this is far lower than what would be needed for creating a realistic in vitro AAA model. Our findings do not support the feasibility of developing an in vitro AAA by enzymolysis followed by passive stretching of the aorta. The findings also suggest that AAA formation is unlikely to be a passive creep-induced stretching of a proteolytically degraded aortic wall as conventional thinking may suggest, but rather may be predominantly due to growth and remodeling of the aortic wall.
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PMID:The effect of proteolytic treatment on plastic deformation of porcine aortic tissue. 1962 9

A reliable estimation of wall stress in Abdominal Aortic Aneurysms (AAAs), requires performing an accurate three-dimensional reconstruction of the medical image-based native geometry and modeling an appropriate constitutive law for the aneurysmal tissue material characterization. A recent study on the biaxial mechanical behavior of human AAA tissue specimens demonstrates that aneurysmal tissue behaves mechanically anisotropic. Results shown in this communication show that the peak wall stress is highly sensitive to the anisotropic model used for the stress analysis. In addition, the present investigation indicates that structural parameters (e.g., collagen fiber orientation) should be determined independently and not by means of non-linear fitting to stress-strain test data. Fiber orientation identified in this manner could lead to overestimated peak wall stresses.
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PMID:The effect of material model formulation in the stress analysis of abdominal aortic aneurysms. 1965 44

Abdominal aortic aneurysm is a multifactorial disease with genetic risk factors and an immunologic component. Immune cells, including macrophages, neutrophils, mast cells, B- and T- lymphocytes, along with vascular smooth muscle cells and adventitial fibroblasts, produce cytokines and enzymes, promoting an inflammatory reaction, extracellular matrix degradation, and neovascularization. Among the different enzymes secreted by immune and stromal cells, matrix metalloproteinase (MMP)-2, MMP-9, MMP-12, cathepsins, and neutrophil elastase cause medial degeneration. Chymase causes smooth muscle cell apoptosis, and MMP-3, MMP-8, and MMP-13 cause adventitial collagen degradation, promoting abdominal aortic aneurysm rupture. At the same time chemokines (interleukin 8, macrophage inflammatory protein 1 alpha, monocyte chemotactic protein-1) cause recruitment and proliferation of inflammatory cells, whereas cytokines (vascular endothelial growth factor and transforming growth factor-beta) promote neoangiogenesis.
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PMID:Immune cells and molecular mediators in the pathogenesis of the abdominal aortic aneurysm. 1969 Apr 70


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