Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type III collagen contributes to the tensile strength of the aortic wall, and mutations in the type III collagen gene have been suggested as the basis for the familial tendency to abdominal aortic aneurysm (AAA). Variation in this gene was investigated in 153 patients with AAA, 87 with aortoiliac stenosis and 98 age-matched controls. The rare mutation at amino acid 619 of Gly-->Arg, previously associated with AAA in a single family, was not found in any of the patients with aneurysm. For the Ala-->Thr variation at amino acid 531, the frequency of the threonine allele was 0.25 in patients with AAA and stenosis, compared with 0.35 in controls. The frequency of the rare allele in the region 3' to the gene demonstrated by Ava II digestion (0.27 in the general population) was found to be 0.29 in the AAA group and 0.19 in the stenosis group (P = 0.023). In the AAA group the presence of the Ava II rare allele was associated with a significant increase in aneurysm diameter (P = 0.044). Non-invasive assessment of aortic distensibility was available in 25 patients: those carrying the Ava II rare allele had less distensible aortas than those not carrying this allele (median pressure-strain elastic modulus 42.0 and 23.9 N/cm2 respectively, P = 0.008). Variation in the type III collagen gene may influence the mechanical properties of the ageing aorta and hence its susceptibility to disease and dilatation. In contrast, there is no evidence for a single common founder mutation in type III collagen predisposing to AAA.
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PMID:Influence of type III collagen genotype on aortic diameter and disease. 824 88

Collagen and elastin are the main extracellular matrix proteins providing the aortic wall with adequate mechanical properties and resistance for proper function. Our study aimed at investigating the relationship between the elastin concentration of the wall of normal and aneurysmal abdominal aortas (AAA), the collagen concentration, and its extractability, as a function of their size. Infrarenal aortas were collected from 30 patients undergoing operative repair of abdominal aortic aneurysm. Age-matched control samples were obtained from eight autopsies of individuals without vascular disease. Samples were divided into five groups according to the aortic diameter: control group (group N, n = 8); < 50 mm (group I, n = 6; between 50-75 mm (group II, n = 10); > 75 mm (group III, n = 7); and ruptured (group IV, n = 7). The collagen concentration in samples from group I was similar to the controls. An increased collagen concentration was observed in group II and remained at the same level in the largest and ruptured aneurysms. Extractability of collagen was found to be increased in group III and was even higher in group IV. A highly significant reduction in elastin concentration was observed in group I and there was progressive reduction with increasing diameter and rupture. A significant correlation could be established between aortic diameter, increased collagen extractability and decreased elastin content.
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PMID:Modifications of the extracellular matrix of aneurysmal abdominal aortas as a function of their size. 827 64

We have experienced graft replacement of a thoracic aortic aneurysm in a 42-year-old man with Ehlers-Danlos syndrome. The patient received graft replacement of the abdominal aortic aneurysm 1 year before this thoracic operation but had no abnormality in his outside appearance. Thoracic CT scan revealed a thoracic aortic aneurysm of 80 mm in maximal diameter. We performed a graft replacement of the thoracic aorta from the ascending aorta to the proximal descending thoracic aorta using deep hypothermia and retrograde cerebral perfusion. The aortic wall was so thin that we used Teflon felt for reinforcement of graft anastomosis at the outside wall of the aortic stump. Type III collagen stain of the resected aortic wall showed deficiency of type III collage, which was consistent with Ehlers-Danlos syndrome (type IV). Postoperative course was uneventful, and the patient returned to his ordinary life.
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PMID:[Successful graft replacement of a thoracic aortic aneurysm in a patient with Ehlers-Danlos syndrome]. 852 72

Knowledge of the biomechanical behavior of abdominal aortic aneurysm (AAA) as compared to nonaneurysmal aorta may provide information on the natural history of this disease. We have performed uniaxial tensile testing of excised human aneurysmal and nonaneurysmal abdominal aortic specimens. A new mathematical model that conforms to the fibrous structure of the vascular tissue was used to quantify the measured elastic response. We determined for each specimen the yield (sigma y) and ultimate (sigma u) strengths, the separate contribution to total tissue stiffness by elastin (EE) and collagen (EC) fibers, and a collagen recruitment parameter (A), which is a measure of the tortuosity of the collagen fibers. There was no significant difference in any of these mechanical properties between longitudinal and circumferential AAA specimens, nor in EE and EC between longitudinally oriented aneurysmal and normal specimens. A, sigma y, and sigma u were all significantly higher for the normal than for the aneurysmal group: A = 0.223 +/- 0.046 versus A = 0.091 +/- 0.009 (mean +/- SEM; p < 0.0005), sigma y = 121.0 +/- 32.8 N/cm2 versus sigma y = 65.2 +/- 9.5 N/cm2 (p < 0.05), and sigma u = 201.4 +/- 39.4 N/cm2 versus sigma u = 86.4 +/- 10.2 N/cm2 (p < 0.0005), respectively. Our findings suggest that the AAA tissue is isotropic with respect to these mechanical properties. The observed difference in A between aneurysmal and normal aorta may be due to the complete recruitment and loading of collagen fibers at lower extensions in the former. Our data indicate that AAA rupture may be related to a reduction in tensile strength and that the biomechanical properties of AAA should be considered in assessing the severity of an individual aneurysm.
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PMID:Ex vivo biomechanical behavior of abdominal aortic aneurysm: assessment using a new mathematical model. 888 38

Abdominal aortic aneurysms (AAAs) are an increasingly common and potentially lethal condition. Surgical repair of AAA is now yet performed quite safely, yet ruptured AAAs still carry mortality rates of 50% to 70%. Ultrasound screening may help identify unsuspected AAA, thereby allowing elective repair. Because AAAs too small to warrant operation still expand progressively, therapeutic approaches to suppress AAA growth would be welcome. Current concepts indicate that AAAs arise through pathophysiologic process distinct from occlusive atherosclerosis and dominated by degenerative changes in the elastic media. These include marked alterations in elastin and collagen, chronic inflammation, and features of autoimmunity, medial neovascularization, and a decrease in vascular smooth muscle cells. Proteinases associated with mononuclear inflammatory cells, particularly matrix metalloproteinases, likely mediate the degradation of structural proteins in the aortic wall. Experimental studies demonstrate that similar processes occur in an elastase-induced rodent model of AAA, providing a means by which to develop novel therapeutic strategies for this disease. Pharmacologic inhibitors of matrix metalloproteinases act to suppress aortic elastin degradation and limit the growth of experimental AAA in vivo, suggesting at least one approach that may be useful in clinical application. Further developments can be expected to increase knowledge of the pathophysiology underlying aortic aneurysm disease, ultimately providing new therapies for small AAAs based on sound understanding of disease mechanisms.
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PMID:Basic science of abdominal aortic aneurysms: emerging therapeutic strategies for an unresolved clinical problem. 888 78

Past concepts of aneurysmal dilatation as a passive process of attenuation are oversimplified and inaccurate. Aneurysm formation is a complex remodeling process that involves both synthesis and degradation of matrix proteins. Interstitial procollagen gene expression is increased in AAA compared to AOD or normal aorta, whereas tropoelastin gene expression is decreased in both AOD and AAA. The medial elastin network is disrupted and discontinuous in small AAA. Thus, the growth rate of an established AAA may well relate to the balance between collagen synthesis and degradation. Although the increased procollagen expression found in AAA may represent a compensatory response, understanding the factors that modulate matrix metabolism in AAA may allow for development of pharmacologic strategies which effectively inhibit the growth of small aneurysms.
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PMID:Biochemistry and molecular regulation of matrix macromolecules in abdominal aortic aneurysms. 895 89

Confluent skin fibroblast cultures were prepared from 40 patients diagnosed with and surgically treated for an abdominal aortic aneurysm. An analysis of secreted type I and type III collagen in the media of these fibroblast preparations revealed reduced secretion of type III collagen from six patients. DNA sequence analysis of the entire coding domain of the pro alpha 1 (III) collagen mRNA in skin fibroblast RNA from these six patients revealed a C to T substitution at nucleotide 607 in one of the probands that would result in the replacement of a leucine residue with phenylalanine in the second position of the first tripeptide repeat in the triple-helical domain of type III collagen. Allele-specific hybridization analysis of genomic DNA from this proband and family members indicated that this non-glycine substitution probably contributed to the aneurysmal phenotype in this patient. No coding sequence mutations were found in the other five patients. It is clear from this study, therefore, that aberrant synthesis of type III collagen, as a consequence of both a coding sequence mutation and other factors contributing to reduced secretion of type III procollagen, will result in the development of an aortic aneurysm in a significant percentage of patients with this disease.
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PMID:Multiple defects in type III collagen synthesis are associated with the pathogenesis of abdominal aortic aneurysms. 895 96

Percutaneous placement of an endovascular stent, with and without coils, in the treatment of large AAA in animal models is feasible, safe and effective. The covered stent sealed off AAA immediately after stent placement, however, it interrupted blood flow into arteries in the area covered by the stent. The uncovered stent prevented further expansion of the aneurysm and also significantly decreased the incidence of rupture. The long-term patency of branch arteries by the uncovered stent supported the possibility of safely using this approach in humans. Furthermore, either covered stent or uncovered stent with additional coils have the potential for treatment of acute aneurysm rupture or leaking. Most importantly, the aneurysm lumen in our model was gradually replaced by collagen after stent placement which further reduces the risk of aneurysm rupture: and this healing process was enhanced by the addition of coils. If proven safe and effective for humans as well, this technique has the potential for substantially reducing the morbidity and mortality associated with AAA.
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PMID:Non-surgical treatment of abdominal aortic aneurysms. 936 37

Changes in copper concentration in the arterial wall are important because of cross-linkage formation in collagen and elastin. The breakdown of the elastic layer is characteristic for aneurysm and is affected by the abnormalities in copper metabolism. This study was undertaken to evaluate Ca, Mg, Zn and Cu concentrations and their relationships in the arterial wall, serum and calcified plaque in atherosclerosis obliterans (AO) and abdominal aortic aneurysm (AA). Samples of the aorta wall were obtained at the endarterectomy in AO and the vascular reconstruction in AA. Elements were determined by means of atomic absorption spectrometry. Serum concentrations of Zn and Cu were higher and that of Ca lower in AO as compared to AA and the controls. Arterial concentrations of Zn, Cu and Mg were higher in AO as compared to AA. The ratios of element concentrations in serum (Ca/Mg, Ca/Zn and Mg/Cu) were higher in serum in AA than in AO. Positive correlations were calculated for Ca and Mg (r > or = 0.74), Ca and Zn (r > or = 0.73), Mg and Zn (r > or = 0.90) in the arterial wall in AO and AA. Low but significant correlation was calculated for Cu concentrations between serum and the arterial wall in AA (r = 0.43). Concentrations of Ca, Mg, Zn and Cu were higher in plaque than in the surrounding tissue. The results indicate differences in arterial and serum concentrations of Ca, Mg, Zn and Cu between AO and AA and the accumulation of these elements in the plaque rather than in the surrounding vascular tissue.
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PMID:Relationship of calcium, magnesium, zinc and copper concentrations in the arterial wall and serum in atherosclerosis obliterans and aneurysm. 957 76

A 47-year-old woman on long-term hemodialysis due to a chronic isolated abdominal aortic dissection was admitted to our department with severe abdominal pain. She had not suffered any hematemesis or melena. An emergency laparotomy revealed an abdominal aortic aneurysm with a diameter of 60mm, densely adhered to the ileum. An aortoenteric fistula manifesting as intramural rupture into the ileum was found after infrarenal abdominal aortic and bilateral common iliac cross-clamping. The fistula on the ileac side was nontransmural, but that on the aortic side communicated with the pseudolumen of the abdominal aorta, and contained mural thrombus. The infrarenal abdominal aorta and bilateral common iliac arteries were replaced with a collagen-sealed woven Dacron bifurcated graft. Histological examination of the ileum in this portion showed intramural bleeding and xanthomatous granulation with foam cell infiltration in the thickened subserosa. While it is difficult to diagnose nonpenetrating aortoenteric fistula preoperatively, such a fistula must be considered in a patient with severe abdominal pain, for whom previous abdominal aortic surgery has been performed or when an abdominal aneurysm is observed. To our knowledge, no other case of an aortoenteric fistula presenting as an intramural rupture into the ileum in an isolated abdominal aortic dissection has ever been reported.
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PMID:Primary aortoenteric fistula with a chronic isolated abdominal aortic dissection: report of a case. 959 Jul 17


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