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)

The hemorrhagic and connective tissue complications of infection with Ebola virus are poorly understood. While searching for homologies and motifs of the aortic aneurysm-associated autoantigenic protein 40 kDa (AAAP-40), we have noted some short sequences (possibly shared epitopes) that occur in the envelope glycoprotein (40 kDa) of the Ebola virus. As a first step toward determining whether molecular mimicry of human matrix proteins by the Ebola virus protein might explain some of the severe connective tissue manifestations of infection, we have tested whether immunoglobulin (IgG) purified from the sera of patients with abdominal aortic aneurysm (AAA) are immunoreactive with the 40-kDa protein of the Ebola virus. Immunoblots of soluble Ebola proteins (strain Mayinga/Zaire) were probed with IgG's purified from the sera of eight patients with AAA and two healthy young control volunteers. The proteins were also probed with IgG extracted from the walls of two surgical aneurysm specimens. Serum IgG from eight consecutively studied AAA patients was immunoreactive with an Ebola virus protein of 40 kDa, consistent with the envelope glycoprotein. IgG's extracted from the walls of two AAAs were also reactive. The control sera were not reactive. In addition to the Ebola sequences in AAAP-40, an Ebola sequence also occurs in the microfibril-associated glycoprotein-4 (MAGP-4), which is distributed ubiquitously throughout connective tissue with elastin. We hypothesize that the catastrophic hemorrhagic and connective tissue complications of Ebola virus infection may be the result of these shared epitopes.
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PMID:A novel hypothesis to explain the hemorrhagic and connective tissue manifestations of Ebola virus infection. 893 9

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

A 6-year-old boy from China presented initially at 2 years of age with a pulsatile mass in his right antecubital fossa. He was not fully evaluated until the age of six years, when pan-angiography and computed axial tomography scan revealed multiple aneurysms of his right brachial artery, right radial artery aneurysms, an infrarenal aortic aneurysm, and a right internal carotid artery aneurysm in the region of the cavernous sinus. The patient underwent uneventful repairs of both the abdominal aortic aneurysm and the multiple aneurysms of the right arm. Pathologic evaluation was significant for medial fibrosis of the arterial wall with decreased and disordered elastin fibers. Review of the previously reported cases in children indicate the upper extremity arteries are involved in 92% of patients, the aortoiliac region in 92% of patients, and the renal/mesenteric vessels in 77% of cases. Lower extremity and cerebrovascular arteries are involved to a lesser extent. Children with peripheral aneurysms should have pan-angiography performed before treatment is begun. Surgical repair in these cases has been excellent.
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PMID:Multiple idiopathic arterial aneurysms in children: a case report and review of the literature. 915 27

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

Degradation of extracellular matrix, especially elastin, within the aortic wall is a hallmark of abdominal aortic aneurysms (AAAs). Normal turnover of matrix proteins is mediated by a family of enzymes called matrix metalloproteinases (MMPs). MMP activity is regulated by proteins called tissue inhibitors of metalloproteinases (TIMPs). We analyzed the expression of all known MMPs with established elastolytic activity and TIMPs in human AAA and control tissue. mRNA coding for MMP-9, MMP-2, human macrophage metalloelastase, MMP-7, TIMP-1, and TIMP-2 were amplified by reverse transcriptase-PCR in control and AAA tissue. A Northern blot assay was used to measure the levels of mRNA coding for MMP-2, MMP-9, TIMP-1, and TIMP-2. Control aortic tissue was obtained from patients with occlusive disease and from organ donors. The expression of MMP-7 and human macrophage metalloelastase was not detected in any aortic specimens. By Northern blot analysis the mean level of MMP-2 mRNA was not significantly different between control groups and AAAs (normalized values: occlusive, 1.5 +/- 0.8, n = 3; donor, 4.5 +/- 2.2, n = 6; AAA, 4.0 +/- 0.95, n = 15). There was a significant increase in the level of MMP-9 mRNA in AAA specimens (occlusive, 16.8 +/- 3, n = 3; donor, 5.7 +/- 1.2, n = 6; AAA, 56.7 +/- 11, n = 15, p = 0.0069). The levels of mRNA coding for TIMP-1 were not significantly different. There was a small but statistically significant increase in TIMP-2 mRNA in AAA tissue. These data support the hypothesis that increased activity of MMP-9, but not MMP-2, is an important factor in the etiology of AAAs. This enhanced MMP-9 activity could then result in degradation of the ECM, leading to aneurysmal dilatation.
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PMID:Expression of matrix metalloproteinases and TIMPs in human abdominal aortic aneurysms. 1007 71

The relationship between atherosclerosis and abdominal aortic aneurysm development is well known. Atherosclerosis cannot explain the whole mechanism. Genetic characters of mechanisms leading to abdominal aortic development is obvious from this study and others. Our study evidences an increased metalloproteases activity in aortic wall proportionally to the size of the abdominal aortic aneurysm. A decrease of aortic wall elastin is evidenced proportionally to the AAA size. Extractable collagen is significantly increased in the aortic wall of patients operated on for aortic rupture.
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PMID:[Mechanism of the growth and rupture of abdominal aortic aneurysm]. 962 40

The objective of this study was to determine the arterial responses to plasma lipid lowering alone or in combination with (1) estrogen replacement therapy or (2) hormone replacement therapy in surgically postmenopausal female monkeys with preexisting atherosclerosis. Eighty-eight female cynomolgus macaques were ovariectomized, fed an atherogenic diet for 24 months, and then assigned by randomized stratification into 4 groups. One group (baseline, n=20) was necropsied at the end of the atherogenic diet period; the remaining 3 groups were fed a plasma lipid-lowering diet (regression) for 30 months. These regression groups were control (diet only), CEE (receiving conjugated equine estrogens alone), and CEE+MPA (receiving CEE and continuous medroxyprogesterone acetate). A previous report described coronary artery functional and histological results; the present report describes biochemical and histological results from the abdominal aorta. Aortic plaque size was not different between groups, similar to previous findings in the coronary arteries. Aortic cholesterol content (milligrams per gram lipid-free dry weight) was lower in the regression groups compared with baseline, both for free cholesterol (mean, control=19.1, CEE=15.7, CEE+MPA=14.4, and baseline=32.7; P<0.001) and for esterified cholesterol (mean, control=18.9, CEE=15.4, CEE+MPA=14.2, and baseline=58.7; P<0.001). This cholesterol efflux could lead to increased plaque stability without changing the physical size of the lesion. Alterations in aortic connective tissue composition were observed in the regression groups. When expressed as a percentage of the lipid-free tissue weight, the aortic elastin content of the control (mean=14.9) and the CEE+MPA (mean=14.0) groups was lower than that of the baseline group (mean=19.0), which was not different from that of the CEE group (mean=15.8). Aortic collagen content, as estimated by hydroxyproline content per milligram of lipid-free tissue, was higher in the control group (mean=67.4) and the CEE+MPA group (mean=66.1) than in the baseline group (mean=56.2; P<0.05). Collagen content of the CEE group (mean=58.9) was not different from that of the baseline group. When the regression groups were considered separately, the aortic collagen content of the CEE group was lower than that of the control group (P<0.05) and tended to be lower than that of the CEE+MPA group (P=0.10), suggesting that CEE therapy (but not CEE+MPA) inhibits potentially detrimental connective tissue alterations that accompany lesion regression. These results have implications for combinations of lipid-lowering and hormone replacement therapies in relation to vascular remodeling and abdominal aortic aneurysm development.
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PMID:Conjugated equine estrogens alone, but not in combination with medroxyprogesterone acetate, inhibit aortic connective tissue remodeling after plasma lipid lowering in female monkeys. 967 78

The objective of the present study was to determine the viscoelastic properties of the common carotid artery in 35 patients with aortic aneurysm before surgery (AAA) (age 71 years, range 61-84), in comparison with 48 patients with essential hypertension (HT: 50 years, range 24-88) and 44 normotensive subjects (NT: 44 years, range 23-85). The second objective was to establish the relations between common carotid artery (CCA) viscoelastic properties and histologic lesions observed on AAA segments, obtained after surgery. CCA diameter was larger and distensibility smaller in AAA patients than in HT and NT. Distensibility of the aortic aneurysm was smaller than that of upstream 'normal' aorta, itself being smaller than control aortas. AAA wall lesions were extensive, associating adventitial and medial fibrosis, elastolysis, smooth muscle rarefaction, neovascularization, inflammation and plaques. The grade of these lesions was not correlated with the mechanical properties of the aorta and CCA; however, they could explain their qualitative alterations. AAA is characterized by severe stiffening and dilatation of large arteries distant from the aneurysm location. Whether this pattern of arterial phenotype is explained by the increase in stiff material (collagen) and the rarefaction of distensible material (smooth muscle and elastin) remains to be determined.
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PMID:[Associations between viscoelastic properties of large arteries and their extracellular matrix composition in abdominal aortic aneurysms in humans]. 1021 30

Abdominal aortic aneurysms (AAAs) represent a chronic degenerative condition associated with a life-threatening risk of rupture. The evolution of AAAs is thought to involve the progressive degradation of aortic wall elastin and collagen, and increased local production of several matrix metallo-proteinases (MMPs) has been implicated in this process. We have previously shown that tetracycline derivatives and other MMP inhibitors suppress aneurysm development in experimental animal models of AAA. Doxycycline also reduces the expression of MMP-2 and MMP-9 by human vascular wall cell types and by AAA tissue explants in vitro. To determine whether this strategy might have a role in the clinical management of small AAA, we examined the effect of doxycycline on aortic wall MMP expression in vivo. Patients were treated with doxycycline (100 mg p.o. bid) for 7 days prior to elective AAA repair, and aneurysm tissues were obtained at the time of surgery (n = 5). Tissues obtained from an equal number of untreated patients with AAA were used for comparison. By reverse transcription-polymerase chain reaction and Southern blot analysis, MMP-2 and MMP-9 were both found to be abundantly expressed in the aneurysm wall. Preoperative treatment with doxycycline was associated with a 3-fold reduction in aortic wall expression of MMP-2 and a 4-fold reduction in MMP-9 (p < 0.05 compared to untreated AAA). These preliminary results suggest that even short-term treatment with doxycycline can suppress MMP expression within human AAA tissues. Given its pleiotropic effects as an MMP inhibitor, doxycycline may be particularly effective in suppressing aortic wall connective tissue degradation. While it remains to be determined whether MMP inhibition will have a clinically significant impact on aneurysm expansion, it is expected that this question can be resolved by a properly designed prospective randomized clinical trial.
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PMID:MMP inhibition in abdominal aortic aneurysms. Rationale for a prospective randomized clinical trial. 1041 28

The pathogenesis of atherosclerosis and abdominal aortic aneurysm involves breakdown of the elastic laminae. Elastolytic cysteine proteases, including cathepsins S and K, are overexpressed at sites of arterial elastin damage, but whether endogenous local inhibitors counterbalance these proteases is unknown. We show here that, whereas cystatin C is normally expressed in vascular wall smooth muscle cells (SMCs), this cysteine protease inhibitor is severely reduced in both atherosclerotic and aneurysmal aortic lesions. Furthermore, increased abdominal aortic diameter among 122 patients screened by ultrasonography correlated inversely with serum cystatin C levels. In vitro, cytokine-stimulated vascular SMCs secrete cathepsins, whose elastolytic activity could be blocked when cystatin C secretion was induced by treatment with TGF-beta(1). The findings highlight a potentially important role for imbalance between cysteine proteases and cystatin C in arterial wall remodeling and establish that cystatin C deficiency occurs in vascular disease.
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PMID:Cystatin C deficiency in human atherosclerosis and aortic aneurysms. 1054 13


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