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

We present the first mathematical model to account for the evolution of the abdominal aortic aneurysm. The artery is modelled as a two-layered, cylindrical membrane using nonlinear elasticity and a physiologically realistic constitutive model. It is subject to a constant systolic pressure and a physiological axial prestretch. The development of the aneurysm is assumed to be a consequence of the remodelling of its material constituents. Microstructural 'recruitment' and fibre density variables for the collagen are introduced into the strain energy density functions. This enables the remodelling of collagen to be addressed as the aneurysm enlarges. An axisymmetric aneurysm, with axisymmetric degradation of elastin and linear differential equations for the remodelling of the fibre variables, is simulated numerically. Using physiologically determined parameters to model the abdominal aorta and realistic remodelling rates for its constituents, the predicted dilations of the aneurysm are consistent with those observed in vivo. An asymmetric aneurysm with spinal contact is also modelled, and the stress distributions are consistent with previous studies.
 ...
PMID:A mathematical model for the growth of the abdominal aortic aneurysm. 1545 32

The pathogenesis of atherosclerosis and abdominal aortic aneurysm involves substantial proteolysis of the arterial extracellular matrix. The lysosomal cysteine proteases can exert potent elastolytic and collagenolytic activity. Human atherosclerotic plaques have increased cysteine protease content and decreased levels of the endogenous inhibitor cystatin C, suggesting an imbalance that would favor matrix degradation in the arterial wall. This study tested directly the hypothesis that impaired expression of cystatin C alters arterial structure. Cystatin C-deficient mice (Cyst C-/-) were crossbred with apolipoprotein E-deficient mice (ApoE-/-) to generate cystatin C and apolipoprotein E-double deficient mice (Cyst C-/-ApoE-/-). After 12 weeks on an atherogenic diet, cystatin C deficiency yielded significantly increased tunica media elastic lamina fragmentation, decreased medial size, and increased smooth muscle cell and collagen content in aortic lesions of ApoE-/- mice. Cyst C-/-ApoE-/- mice also showed dilated thoracic and abdominal aortae compared with control ApoE-/- mice, although atheroma lesion size, intimal macrophage accumulation, and lipid core size did not differ between these mice. These findings demonstrate directly the importance of cysteine protease/protease inhibitor balance in dysregulated arterial integrity and remodeling during experimental atherogenesis.
 ...
PMID:Cystatin C deficiency increases elastic lamina degradation and aortic dilatation in apolipoprotein E-null mice. 1565 70

Vascular smooth muscle cells (VSMCs) synthesize elastin (ELN), major protein of aortic tunica media which confers strength and elasticity to aortic wall. Protein loss or distortion is typical in aneurysm tunica media. Transforming growth factor beta1 (TGFbeta1) inhibits growth and connective protein expression of abdominal VSMCs cultures. Also, in atherogenic studies, estrogen (but not estrogen plus progestin) treatments inhibit aortic collagen accumulation and elastic loss, risk factors to subsequent aortic enlargement. Therefore, polymorphisms of ELN, estrogen receptor alpha (ERalpha) and beta (ERbeta), progesterone receptor (PR) and TGFbeta1 genes and their products may be involved in the abdominal aortic aneurysm (AAA) development. Using PCR-RFLP method, we analyzed ELN RmaI (exon 16), ERalphaPvuII-XbaI (intron 1), ERbetaAluI (exon 8), PR TaqI (intron 7) and TGFbeta1 Bsu36I (-509 bp, promoter) polymorphisms in 324 Caucasian male subjects: 225 healthy controls (mean age 71.20 +/- 6.85 years) and 99 unrelated AAA patients (mean age 69.8 +/- 7.1 years). No difference in ELN, ERalpha, PR and TGFbeta1 allele frequencies was observed in AAA patients versus controls (P > 0.05). However, because possessing at least an ERbetaAluI restriction site was statistically associated to AAA onset (chi(2) = 5.220; OR = 1.82, P < 0.05), ERbeta polymorphism was proposed as genetic determinant in the AAA susceptibility.
 ...
PMID:Allelic genes involved in artery compliance and susceptibility to sporadic abdominal aortic aneurysm. 1569 46

Multiple arterial aneurysms are distinctly rare in the pediatric population. Most arterial aneurysms in children are secondary to infections, trauma, arteritides, collagen vascular diseases, and other causes. True idiopathic aneurysms are the least common and less than a dozen reports of multiple idiopathic aneurysms have been published. We present a case of an idiopathic, symptomatic renal artery aneurysm with fistulization to the renal vein and a concomitant abdominal aortic aneurysm in a 6-year-old boy. The diagnostic workup, surgical treatment, pathologic findings, and a review of the literature are presented.
 ...
PMID:Idiopathic renal artery and infrarenal aortic aneurysms in a 6-year-old child: case report and literature review. 1588 77

The cysteine protease cathepsin L is one of the most potent mammalian elastases and collagenases, widely expressed at basal levels in most tested tissues and cell types, and regulated by pro-inflammatory stimuli. The inflammatory arterial diseases abdominal aortic aneurysm (AAA) and atherosclerosis involve extensive vascular remodeling that requires elastolysis and collagenolysis. This study examined the hypothesis that cathepsin L is over-expressed in human AAA and atherosclerotic lesions and its expression in vascular cell types found in these lesions is regulated by pro-inflammatory cytokines. Immunohistochemical and tissue extract immunoblot analysis demonstrated increased expression of cathepsin L in human AAA and atheromata and localized its expression to lesional smooth muscle cells (SMC), endothelial cells (EC), and macrophages. In primary cultured human SMC, EC, and monocyte-derived macrophages, pro-inflammatory cytokines or growth factors induced the expression of cathepsin L and its activity against extracellular collagen and elastin. Patients with coronary artery stenosis (n=65) had higher serum cathepsin L levels than those without lesions detectable by quantitative coronary angiography (n=30) (1.47+/-0.33 ng/ml versus 0.60+/-0.06 ng/ml, p<0.02). A strong correlation between the percent of stenosis of left anterior descending coronary artery and serum cathepsin L levels in patients with stenosis (R=0.542, p<0.0001), also suggests involvement of cathepsin L in these vascular diseases.
 ...
PMID:Cathepsin L expression and regulation in human abdominal aortic aneurysm, atherosclerosis, and vascular cells. 1598 60

Abdominal aortic aneurysm (AAA) is characterized by dilatation of arterial walls, which is accompanied by degradation of elastin and collagen molecules. Biochemical and environmental factors are known to be relevant for AAA development, and familial predisposition is well recognized. A connective tissue disorder that is also associated with fragmentation of elastic fibers is Pseudoxanthoma elasticum (PXE). PXE is caused by mutations in the ABCC6 gene and mainly affects dermal, ocular and all vascular tissues. To investigate whether variations in ABCC6 are found in AAA patients and to determine mutations in PXE patients, we analyzed seven selected ABCC6 exons of 133 AAA and 54 PXE patients subjected to mutational analysis. In our cohort of AAA patients, we found five ABCC6 alterations, which result in missense or silent amino acid variants. The allelic frequencies of these sequence variations were not significantly different between AAA patients and healthy controls. Therefore, we suggest that alterations in ABCC6 are not a genetic risk factor for AAA. Mutational screening of the PXE patients revealed 19 different ABCC6 variations, including two novel PXE-causing mutations. These results expand the ABCC6 mutation database in PXE.
 ...
PMID:Analysis of sequence variations in the ABCC6 gene among patients with abdominal aortic aneurysm and pseudoxanthoma elasticum. 1612 78

The abdominal aortic aneurysm (AAA) wall represents an extreme example of arterial remodeling with disturbed elastin, collagen and proteoglycan metabolism. The aim of this study was to evaluate enzymes involved in the degradation of glycosaminoglycan chains and core proteins of proteoglycans in the AAA wall. The study material consisted of wall samples from 10 AAA. Fragments of 5 normal abdominal aortas from organ donors were used as a control. The activity of endoglycosidases, exoglycosidases and sulfatases was measured using colorimetric methods. To assess matrix metalloproteinases (MMPs), Western blot and zymography were performed. The activity of endoglycosidase degrading chondroitin-4-sulfate was lower in the AAA wall. Endoglycosidase degrading heparan sulfate and dermatan sulfate, arylosulfatase B, as well as all the exoglycosidases assessed demonstrated higher activities in the AAA wall. Furthermore, increased expression of MMP1, MMP2 and MMP9 was also shown in the AAA wall. Zymography revealed decreased activity of pro-MMP2 and presence of pro-MMP9 in the AAA wall compared to the wall of normal aorta. Extensive changes in the activity of glycosaminoglycan-degrading enzymes and MMPs may influence the organization of the extracellular matrix network and lead to previously demonstrated changes in the proteoglycan and glycosaminoglycan content in the AAA wall.
 ...
PMID:Evaluation of enzymes involved in proteoglycan degradation in the wall of abdominal aortic aneurysms. 1629 69

The purpose of this work was to develop an abdominal aortic aneurysm (AAA) model that resembles human aneurysms with potential for further growth, patent collateral vessels, and a predictable tendency to rupture, and that can be used in the development of new endoprostheses and implant training. An infrarenal AAA model was created in five domestic swine using an autologous gastric serosal patch. Pre- and postsurgical digital subtraction aortograms (DSA) were obtained to document the appearance and dimensions of the aneurysm. Animals were followed up with DSA and ultrasonography on days 7, 14, 30, 45, 60, and 90 after model creation. Aneurysmal diameters were measured with both techniques in all examinations. On day 90, animals were euthanized, target arteries were harvested, and pathological evaluation was performed. The nonparametric Wilcoxon test was used to assess any differences in measured diameters. All the animals survived the surgical procedure. The aneurysmal diameters increased from 8.14+/- 2.15 to 13.28+/- 1.18 mm immediately after surgery (p < .05), but no subsequent significant growth of the aneurysmal sac was seen during follow-up. In this experimental setting, measurements obtained with DSA were slightly larger than those obtained with ultrasound. Two animals died of AAA rupture on days 6 and 10 (40% rupture rate). Pathological examination showed lack of elastic laminae and increased collagen content in the aortic patch. Thus, model showed a tendency to rupture, but no significant potential for further aneurysmal growth. It might be useful for training in endovascular therapies, but its usefulness for preclinical endovascular device testing is limited by its lack of growth potential.
 ...
PMID:A new model of abdominal aortic aneurysm with gastric serosa patch: surgical technique and short-term evaluation. 1653 67

A 70-year-old man with abdominal aortic aneurysm underwent surgical repair with Hemashield vascular graft. Postoperatively, he was found to have very low plasma cortisol levels, which failed to increase after stimulation with ACTH. A tentative diagnosis of adrenal insufficiency was made despite the lack of its clinical manifestations and a replacement therapy with hydrocortisone was started. He had also elevated plasma levels of TSH, thyroid hormones and estrogen without any clinical manifestations. Such abnormal hormone levels were spontaneously normalized three months after operation, which was later proven to be factitious by different immunometric assays (IMA). Since the vascular graft coated with bovine type I collagen has been reported to induce a transient immune response in some patients after surgery, we speculated that certain antibodies generated against heterologous collagen and/or yet-unknown components derived from the graft may have caused such factitious data; exogenous addition of bovine type I collagen and albumin to patient's serum, however, failed to affect the assay results. Whatever the cause, caution must be paid that some patients with surgical repair using heterologous materials may have such factitious hormone data by IMAs.
 ...
PMID:A case of factitious adrenal insufficiency after vascular graft surgery caused by spurious immunometric assays. 1672 10

Problems of displacement, poor healing, degradation of the polymers and corrosion of the metallic frame in endovascular devices still require in-depth investigations. As the tissues and the foreign materials are in close contact, it is of paramount importance to efficiently investigate the interfaces between them. Inclusion in polymethymethacrylate (PMMA) permits us to obtain thin slides and preserve the capacity to perform the appropriate stainings. An AneuRx prosthesis was harvested in bloc with the surrounding tissues at the autopsy of a patient 25 months post deployment in a 5.7 cm diameter AAA and sectioned in the direction of the blood flow in two halves. A cross-section of the encapsulated distal segment together with the surrounding aneuryshmal sac was embedded in polymethylmethacrylate (PMMA). Further to complete polymerization, slices of the specimen were cut on a precision banding saw under coolant. They were affixed onto methacrylate slides with a UV cured adhesive. Binding and polishing were done on a numeric grinder and slices 25 to 30 microm in thickness were stained with toluidine blue prior to observation in light microscopy. Additional slices were prepared for scanning electron microscopy and X-ray energy dispersive spectrometry for determination of the elemental composition of the Nitinol stent. The aortic wall did not demonstrate complete integrity along with its circumference. Some areas of rupture were noted. The content of the sac was heavily shrunk and was mostly acellular. The walls of the device were very well encapsulated. The PMMA embedding permitted the polyester wall, the Nitinol wire and the collagen to keep in close contact. Scanning electron microscopy involved backscattered electrons and confirmed the corrosion the Nitinol wire at the boundary with living tissues. Based upon the results obtained, we believe that PMMA embedding is the most appropriate method to process endovascular devices for histological and material investigation. Needless to say, that paraffin embedding would have not been feasible for such a big size specimen involving different materials.
 ...
PMID:Polymethylmethacrylate (PMMA) as an embedding medium preserving tissues and foreign materials encroaching in endovascular devices. 1680 35


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>