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

Smooth muscle cells (SMC) were obtained by outgrowth of human aortic explants from abdominal aortic aneurysm (AAA) patients, aortic occlusive disease (AOD) patients, and transplant donors (controls). Specimens were incubated with medium alone or medium with either elastin-derived peptides (EDP, 5 micrograms/mL) or low-density lipoproteins (LDL, 5 micrograms/mL). Elastase activity (ng/mg total protein) was assayed from 4-week-old cultures. Control aortas obtained from patients significantly younger secrete an increased amount of elastase at baseline compared with AOD and AAA patients (p less than 0.05). Elastin-derived peptides caused a significant increase in elastase secretion in all groups. The increase in elastase secretion in response to EDP in AAA patients was significantly higher compared with AOD or control. Low-density lipoprotein had no effect on SMC elastase secretion. These data suggest that (1) aortic SMCs secrete elastase in response to EDP, (2) SMC elastase is age dependent, and (3) AAA SMC secrete an abnormally high amount of elastase compared with AOD and control aortas in response to EDP. Like the neutrophil, the SMC is highly responsive to the degradation products of elastin and in AAA patients secrete significantly increased amounts of elastase in response to the breakdown products of atherosclerosis.
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PMID:Smooth muscle cell elastase, atherosclerosis, and abdominal aortic aneurysms. 141 82

Although elastin depletion is thought to be an etiologic factor in abdominal aortic aneurysm, little is known about its transcription and posttranslational modification in normal and diseased human aorta. Our objectives were to quantify total elastin and elastin cross-links (desmosine/isodesmosine [DID]) and to determine if elastin mRNA was detectable in the disease-prone infrarenal aorta from patients with abdominal aortic aneurysm and a comparative group with no aneurysmal diseases. After preliminary extraction and thermolysin digestion, content of DID and the elastin tetrapeptide, valine-alanine-proline-glycine (VAPG), were determined by high-performance liquid chromatography. Tissue mRNA was studied by Northern blot analysis. Mean values (+/- SE) were compared by Student's t test. The proportion of insoluble elastin was markedly decreased in abdominal aortic aneurysm tissue (1.3% +/- 0.04% vs 12% +/- -2.8%; p less than 0.001). There was no difference in the small percentage of elastin solubilized during extraction in abdominal aortic aneurysm (5.3% +/- 1%) and no aneurysmal disease (6.0% +/- 1.2%; p = 0.71) tissues. The DID concentration of insoluble elastin was not different for abdominal aortic aneurysm and no aneurysmal disease tissue (0.18% +/- 0.07 vs 0.18 +/- 0.05 nm DID/nm VAPG; p = 0.97). On the basis of VAPG content, only 26% +/- 4% of the sodium hydroxide insoluble residue from abdominal aortic aneurysm was elastin; the predominate protein(s) was high in polar amino acids. Elastin mRNA was detectable in all tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elastin content, cross-links, and mRNA in normal and aneurysmal human aorta. 149 42

At age 3 years, WHHL rabbits are near the end of their lifespan, frequently dying from the progression of their hyperlipidemic disease from events such as myocardial infarction. Out of a colony of 20 three-year-old WHHL rabbits raised as part of a NIH breeding project, 2 rabbits actually died of a ruptured thoracic aortic aneurysm. The need for a model to study abdominal aortic aneurysm formation led us to explore further the abdominal aortic pathology in aged WHHL rabbits. Six rabbit abdominal aortas from 3-year-old WHHL rabbits were preserved in formalin, sectioned, and stained for elastin. These were compared to the same sections of six normolipidemic age matched New Zealand white (NZW) rabbits. There was significant (P less than or equal to .001) destruction of the medial lamellar elastin unit in the aorta of the WHHL rabbits compared with the control NZW rabbits. Severe cholesterol deposits appeared to destroy the medial lamellae from the inside out. No definite aneurysm formation was seen in the abdominal aorta despite the significant changes in the medial lamellar elastin units. Thus, this model could be used to study the elastin degeneration of the media, but not necessarily abdominal aortic aneurysm formation.
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PMID:Watanabe hyperlipidemic rabbit as a model of aortic degeneration of the medial lamellar elastin unit. 157 2

To test the hypothesis that elastin-derived peptides (EDP) from human aortic tissue may be chemotactic for inflammatory cells, we studied the chemotaxis of neutrophils and monocytes to EDP derived from abdominal aortic aneurysm (AAA), aortic occlusive disease (AOD), and control aortas. In addition, we determined if neutrophils deliver neutrophil elastase to the aorta in vivo by staining for neutrophil elastase (NE) throughout the course of abdominal aortic aneurysms with the monoclonal antibody to human NE. EDP from AAA, AOD, and control tissue demonstrated significant chemotactic activity for both neutrophils and monocytes. All neutrophils had a greater attraction to EDP from AAA tissue compared to AOD and control aorta. Neutrophils from AAA patients were more attracted to EDP of AAA tissue than were neutrophils of AOD or control patients attracted to their respective aortic EDP. Neutrophil elastase stained positive in the adventitia and thrombus throughout the course of the aneurysm, but was not found in the intima, media, or plaque of the aorta.
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PMID:Neutrophil chemotaxis and neutrophil elastase in the aortic wall in patients with abdominal aortic aneurysms. 177 36

Fifty-two cases of abdominal aortic aneurysms including common iliac aneurysms operated on during July, 1981 and December, 1989 have been studied. They were divided into the following three of elective operation (n = 34), impending rupture (n = 5), and ruptured (n = 13) groups. Cases with abdominal operations without aneurysms were randomly selected as the control group (n = 12). Overall operative mortality was 9.6%, consisted of 30.8% of the ruptured, 20.0% of the impending rupture and 0% of the elective operation groups. Respiratory functions including FEV1.0%, V75, V50, V25 and V25/Ht were significantly lowered in the ruptured group. PaO2 of the ruptured group was also significantly lowered in comparison with both the control and the elective operation groups. Leukocytic granular elastase, playing a role of destruction of the elastin component in the pulmonary alveoli and the aortic media, was increased in the patients with ruptured aortic aneurysms, though the difference was not significant. The data suggested the possibility of aneurysm rupture in case with elevated leukocytic granular elastase. Surgery for abdominal aortic aneurysm, even in cases with decreased pulmonary function, should be considered aggressively to elimination of ominous result of aneurysm rupture.
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PMID:[A retrospective study of ruptured abdominal aortic aneurysms--association with respiratory function and leukocytic granular elastase]. 188 80

1. There is a familial tendency to abdominal aortic aneurysms. We have followed up a previous report of a weak association between the haptoglobin 2-1 phenotype and aortic aneurysm and investigated polymorphisms of the haptoglobin gene and neighbouring cholesterol ester transfer protein gene on the long arm of chromosome 16 in patients with atherosclerotic abdominal aortic aneurysm, patients with stenosing aortic atherosclerosis and healthy control subjects. The protein polymorphism of haptoglobin results from variant alpha-chains, alpha 1 and alpha 2, the phenotype nomenclature describing the two alpha-chains. We have also investigated whether the different haptoglobin phenotypes influence the degradation of aortic connective tissue. 2. The frequency of the haptoglobin alpha 1 allele was increased in patients with aneurysms compared with healthy control subjects (0.51 versus 0.35, P less than 0.05). Patients homozygous for the alpha 2 allele had the highest mean age at aneurysm resection. The frequency of a rare polymorphism at the cholesterol ester transfer protein locus was also increased in aneurysm patients (0.15 versus 0.05 in control subjects, P less than 0.01). These two genetic markers appear to act independently. Haptoglobins containing an alpha 1-chain accelerated two- to four-fold the degradation by elastases of aortic elastin in vitro. 3. Genetic variation in the haptoglobin and cholesterol ester transfer protein genes appears to influence dilatation of the abdominal aorta. Variation at the haptoglobin locus could have a direct effect on the degradation of elastin in atherosclerotic aorta, whereas variation at the cholesterol ester transfer protein locus could affect lipid metabolism and promote atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Genetic variation on chromosome 16 is associated with abdominal aortic aneurysm. 196 66

Eight cases of inflammatory abdominal aortic aneurysm (IAAA) (group I) and a control group of ten cases of atherosclerotic abdominal aortic aneurysm (AAA) with little or no parietal inflammatory infiltrate (group II) were studied; using light microscopy, transmission electron microscopy (TEM), and immunohistochemistry. These were used to define cell composition in the inflammatory process, the degree of cell activation and alteration of connective tissue. Large numbers of B lymphocytes were present in IAAA with preservation of the T4/T8 ratio. In addition, HLA-DR and the IL2-R antigen (specific for activated cells) were widely expressed in the cell population. The interstitial matrix contained deposits of IgG, IgM and C3c together with an increase in type III collagen and a reduction in elastin which appeared fragmented and swollen. This study, therefore, characterised the cellular component of the parietal inflammatory infiltrate in IAAA. The degree of activation shown by these cell elements and the activation of complement suggest that the relevant antigen may have been localised in the aneurysm wall at the time of observation.
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PMID:The cellular component in the parietal infiltrate of inflammatory abdominal aortic aneurysms (IAAA). 200 88

The predominant pathologic feature of abdominal aortic aneurysm is elastin destruction, and elastin destruction may be mediated by inflammation. In this investigation serial sections of abdominal aortic aneurysm specimens were selectively stained to study the relationship between inflammation and elastin degradation. In addition, soluble aortic extracts were examined for the presence of immunoglobulins. An inflammatory infiltrate was present in 8 of 10 of the abdominal aortic aneurysm specimens examined. The infiltrate was mononuclear, commonly located at the junction of the media and adventitia; it did not codistribute with loss of elastin. The presence of an inflammatory component in abdominal aortic aneurysm was associated with a large amount of immunoglobulin in soluble extracts from aneurysmal tissue compared to atherosclerotic and normal control extracts. This study further characterizes the microscopic pathology of abdominal aortic aneurysm and describes the presence of immunoglobulin in soluble tissue extracts. In addition, the possible role of inflammation in abdominal aortic aneurysm as it relates to protease expression is detailed.
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PMID:The role of inflammation in nonspecific abdominal aortic aneurysm disease. 206 15

A spontaneously aneurysm-prone mouse has a mutation on the X chromosome, which results in an abnormality of copper metabolism. A deficiency of the copper metalloenzyme, lysyl oxidase, results in a deficiency of lysyl-derived cross-linkages in collagen and elastin. Homology of the X chromosome suggests that this model may be relevant to the human abdominal aortic aneurysm (AAA). The present studies on skin from eight AAA patients suggest that copper deficiency occurs in humans, by comparison to skin of paired control subjects with atherosclerotic occlusive disease of the aorta. The lysyl-derived cross-linkage pyridinoline (or some compound with similar ion exchange elution characteristics) is also deficient in patients with AAA; while there is an excess of one of the cross-linkage precursors, hydroxylysine. In addition, the fluorescent properties of hydrolysates of skin from the patients with AAA differ from those of the controls, suggesting that simple biochemical markers might be defined on the basis of these differences in the future. These experiments support the hypothesis that the mouse model is relevant to the disease as it occurs in humans.
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PMID:Deficiencies of copper and a compound with ion-exchange characteristics of pyridinoline in skin from patients with abdominal aortic aneurysms. 687 35

We now know our past concepts of AAA pathogenesis to be oversimplified and inaccurate. In fact, the metabolic activity of the aneurysm wall is markedly increased in comparison with normal aorta. It has become clear that AAAs result not from passive dilatation, but from a complex remodeling process involving both the synthesis and degradation of matrix proteins. Our understanding of this process has been advanced by applying molecular biology techniques. Although elastin fragmentation and medial attenuation remain the most striking histological features of AAA tissue, experimental and clinical evidence suggests that the adventitia, which is predominantly collagen, is capable of maintaining the dimensional stability of the aorta in the absence of the medial elastin network. Thus, although factors that result in fragmentation and attenuation of elastin may be important in the etiology of AAA, factors regulating the balance of collagen synthesis and degradation likely determine the rate of AAA progression. The resident inflammatory cells in AAA undoubtedly play an important pathological role in aortic dilatation. Thus, understanding the interaction between aortic mesenchymal cells (smooth muscle cells and fibroblasts) and inflammatory cells (lymphocytes and macrophages) should allow for the identification of genetic factors that predispose to AAA. In addition to the possibility of early identification of patients at risk for AAA, new insights into AAA pathogenesis might allow for development of pharmacological strategies for inhibiting expansion of small AAA.
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PMID:Pathogenesis of aneurysms. 767 Jun 68


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