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

The pathogenesis of abdominal aortic aneurysm involves many factors acting over time. However, destruction of elastin in the aortic wall is a key event that shifts the load produced by blood pressure on to collagen. This is exacerbated in the presence of hypertension. Smoking and age are further important factors, as is the site; elastic lamellae are relatively less common in the abdominal aorta. Once the shielding effect of elastin is lost, further dilatation and rupture of the aorta depend on the physical properties of the collagen present.
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PMID:Pathogenesis of abdominal aortic aneurysm. 792 83

The decrease in elastin concentration in abdominal aortic aneurysm (AAA) has been ascribed to elastolysis. The discordant response of the elastin and collagen genes in AAA suggests a different explanation: dilution of elastin because of higher levels of synthesis of collagen and other matrix proteins. The purpose of this study was to determine circumferential content of elastin, collagen, and total protein in aneurysmal (AAA), atherosclerotic, and normal (NL) infrarenal aorta. Standard serial extraction techniques of complete 1-cm rings of midinfrarenal aortic tissue were used to remove soluble protein, calcium, and lipids. Hydroxyproline (collagen), desmosine/isodesmosine (elastin), and total amino acid (total protein) content were determined by amino acid analysis. Means values (+/- SEM) were compared by ANOVA. Circumferential content of desmosine/isodesmosine was increased 2.5-fold in AAA compared to NL (P < 0.05). Collagen and total protein were increased 5.7- and 4.7-fold, respectively (P < 0.05). There was a high degree of correlation between circumference and collagen content (r = 0.89). These data demonstrate that significant synthesis of matrix proteins accompanies aortic dilatation. While both elastin and collagen are increased, there is a much greater increase in circumferential collagen content than elastin content. These data do not preclude proteolysis as a factor in AAA but suggest that the decrease in elastin concentration results from dilution of elastin by a greater increase in the synthesis of other matrix proteins and that synthesis is an important factor in AAA formation.
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PMID:Elastin is increased in abdominal aortic aneurysms. 793 21

One of the most consistent observations in abdominal aortic aneurysm (AAA) disease is the disorganization and disruption of elastin and other matrix components of the aortic wall. The enzymatic basis for the biochemical features of AAA has been investigated beginning with the demonstration on substrate gel enzymography of a typical "profile" of proteinase activities in AAA tissue extracts which degrade gelatin, casein and elastin. A recombinant TIMP-1 affinity column was developed and three of the elastolytic/caseinolytic activities with approximate molecular weights of approximately 80 kDa, approximately 50 kDa and approximately 32 kDa were partially purified from these extracts. Affinity for rTIMP-1 suggests that these enzymes are members of the matrix metalloproteinase (MMP) family. High molecular weight forms of two MMPs, collagenase (MMP-1) and stromelysin-1 (MMP-3), were also isolated from the AAA tissue on this column; active forms of MMP-1 could be demonstrated by immunoblotting techniques in this preparation under reducing conditions. Infiltrating inflammatory cells are known sources of these proteolytic activities; analysis of these cell populations in the aneurysmal aortic wall using fluorescence-activated cell counting revealed a fifty-fold increase in macrophages (a well-known source of matrix-degrading enzymes) as well as a significant increase in lymphocytes.
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PMID:Matrix metalloproteinases in abdominal aortic aneurysm: characterization, purification, and their possible sources. 795 5

A prominent metalloproteinase activity with an apparent molecular mass of 80 kD and additional activities at 67 through 70, 50, and 32 kD have been observed on casein, gelatin, and elastin gel zymography in extracts from abdominal aortic aneurysms (AAAs). The forms at 80, 50, and 32 kD were isolated by affinity to recombinant tissue inhibitor of metalloproteinases, and the 80-kD and 50-kD components were shown to be derived from matrix metalloproteinase-9 (MMP-9). The relative electrophoretic mobility of these forms under reducing and nonreducing conditions corresponds to those of MMP-9 generated by MMP-3 (stromelysin-1) cleavage, and the active forms of MMP-3 at 45 and 35 kD were detected in aneurysmal extracts under reducing conditions by using specific antibody. Confirmation that the major proteolytic activity observed at 80 kD is MMP-9 was also demonstrated by immunoprecipitation of the activity with specific antibody. Comparative immunoblots of tissue extracts from 10 typical AAA patients, using specific antibody against MMP-9, revealed bands at 92, 82, 67, 51 through 53, 27, 23, and 20 kD under reducing conditions; six aortic control specimens displayed negligible immunoreactivity. This report is the first to show that known activated forms of MMP-3 and MMP-9 are present in the aneurysmal aortic wall and that they may play a role in the destruction of aortic matrix in AAA disease.
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PMID:Identification of matrix metalloproteinases 3 (stromelysin-1) and 9 (gelatinase B) in abdominal aortic aneurysm. 804 93

Elastase release by neutrophils has been implicated in the etiology of abdominal aortic aneurysm (AAA). The present study investigated whether neutrophils in patients with AAA actively synthesize the neutrophil elastase enzyme and the effect of elastin-derived peptides on neutrophil elastase release. Total neutrophil elastase in patients with AAA was significantly higher than in those with aortic occlusive disease and controls. The neutrophil elastase gene was not expressed in any patient group. Elastin-derived peptides induced elastase release, which was significantly higher in patients with AAA than in those with aortic occlusive disease and controls. These data indicate that the peptides of elastin degradation stimulate the release of elastase, but that continuing production of elastase is absent in circulating neutrophils. It is concluded that: (1) neutrophils do not actively synthesize elastase but act as 'mules' or carriers of the enzyme; and (2) elastin breakdown products stimulate the release of elastase at the aortic wall by circulating neutrophils, which in patients with AAA have a predetermined increased amount of elastase.
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PMID:Role of the neutrophil in abdominal aortic aneurysm development. 807 62

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

Vascular diseases are frequently associated with changes in the mechanical properties of the arterial wall. Existing techniques for studying arterial geometry and mechanical properties in vitro are often destructive, since they involve sectioning of the specimen into strips, or provide average measurements of the mechanical properties over the volume of intact specimens. We developed a high-resolution computed tomography (CT) scanner for in vitro studies of arterial geometry and static elastic properties. The x-ray image intensifier based system can acquire single transverse images, or a volume image, with 2 mm-1 resolution. Images were obtained through an intact abdominal aortic aneurysm at five pressures. The incremental circumferential Young's modulus E(inc) was calculated from the internal and external circumferences, and at physiological pressures E(inc) of the aneurysm was found to be 275 times greater than that of the normal aorta proximal to it. A volume image of the specimen provided landmarks that allowed histological sections to be obtained at locations coincident with those where the elasticity was measured. The histological analysis revealed a sixfold decrease in elastin content in the aneurysm, compared to the normal aorta. We have demonstrated that the static mechanical properties and geometry of vascular specimens can be quantified in vitro with the new high-resolution CT scanner and can be compared subsequently with histological analysis to provide further insight into the understanding of atherogenesis.
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PMID:Elasticity and geometry measurements of vascular specimens using a high-resolution laboratory CT scanner. 840 Dec 67

Abdominal aortic aneurysms (AAAs) have traditionally been attributed to atherosclerosis, although there is increasing epidemiological, biochemical and genetic evidence that aneurysmal arterial disease is different from occlusive atherosclerosis. One of the most consistent biochemical findings in the aneurysmal aorta is a significant reduction in elastin protein; the cause, for this remains unclear. There is in vitro evidence that vitamin D3 (1,25 dihydrocholecalciferol) inhibits the production of elastin by smooth muscle cells. On the basis of this observation and the possibility that some subjects may be exposed to excess vitamin D3, the hypothesis that vitamin D3 may be a previously unrecognized aetiological factor in the pathogenesis of AAA is developed.
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PMID:The role of vitamin D3 in the aetiology of abdominal aortic aneurysms. 852 70

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


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