UMLS:C0162871 - FACTA Search

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

Previous findings vary regarding the timing and cause of elastin fiber degeneration in the elastase-induced rat abdominal aortic aneurysm model. We examined the timing and cause of elastin fiber degeneration after elastase infusion using two different elastase infusion times. Twenty-four Sprague-Dawley rats were divided into two groups. The infrarenal abdominal aorta was infused with 15 U of elastase for 15 min (n = 12, 15-min infusion group) or 30 min (n = 12, 30-min infusion group). In each group, three rats were killed immediately and 1, 3, and 7 days after infusion, and then the aortas were excised for a histologic examination. Elastin fibers did not stain, even immediately after elastase infusion, in the 30-min infusion group. The degeneration of elastin fibers did not progress in the 15-min infusion group during the period of observation. Inflammatory cells infiltrated mainly to the adventitia near regions where the degeneration of elastin fibers spread totally through the aortic media. Elastin fibers degenerate immediately after elastase infusion and thus seem to degenerate not due to endogenous proteinases that are produced by the infiltrating cells, but due to the exogenously infused elastase itself. Inflammatory cell infiltration was thus found to be a result of the degeneration of elastin fibers in this model.
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PMID:The time course of elastin fiber degeneration in a rat aneurysm model. 1095 37

Abdominal aortic aneurysms (AAAs) are characterized by structural alterations of the aortic wall resulting from degradation of collagen and elastin. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, show strong elastinolytic activity. We examined the levels of mRNA for MMP-2, MMP-9, membrane type (MT)-MMP-1, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in AAAs (n = 8), atherosclerotic occlusive diseases (AOD) (n = 8), and normal subjects (n = 8) using the reverse transcription-polymerase chain reaction (RT-PCR). We also analyzed the gelatinolytic activity of these metalloproteinases using gelatin zymography. The levels of MMP-2 and MMP-9 mRNA were increased in the AAA group compared with those in the AOD group and normal subjects. The levels for TIMP-1 and TIMP-2 mRNA in the AAA group were also higher than those in the AOD and normal groups. Only in the case of MT-MMP-1 was the difference between AAA and AOD not statistically significant. By gelatin zymography with the same samples used for RT-PCR, gelatinolytic activity of MMP-9 was elevated in all AAA tissues. The 62-kDa form of MMP-2 was elevated in both the AAA and AOD groups and did not differ significantly between them. Linear regression analysis demonstrated a significant positive correlation between mRNA levels of MMPs and those of TIMPs. These observations suggest that aneurysm formation in patients with atherosclerosis is related to the degree of MMP-9 expression.
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PMID:Enhanced expression of matrix metalloproteinase-9 in abdominal aortic aneurysms. 1134 73

To investigate the role of genetic factors on susceptibility to atherosclerotic arterial disease, the influence of haptoglobin phenotypes (Hp) on serum elastase activity, neutrophil count, and elastin concentration in the aorta was measured in patients with abdominal aortic aneurysm (AAA; n=52) and aortoiliac atherosclerotic occlusive disease (AOD; n=37). Findings (serum elastase activity, peripheral blood neutrophil count) were compared to a control group (CG) of 37 subjects without atherosclerosis. Hp phenotyping performed by starch-gel electrophoresis produced a haptoglobin-hemoglobin complex of three phenotypes: Hp1-1, Hp2-2, and Hp2-1. Distribution of Hp phenotypes was similar in the three study groups (AAA, AOD, CG). Significant increases in serum elastase activity and neutrophil count was measured in Hp2-1 phenotype of AAA patients. Although the aorta wall of aneurysm patients contained less (p<0.001) elastin than that of AOD patients, no significant difference of aorta elastin concentration between the three Hp phenotypes, including Hp2-1, was measured. The postulated association of AAA susceptibility with Hp2-1 phenotype was supported by the study data that demonstrated an increase in serum elastase activity in patients undergoing AAA repair.
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PMID:Abdominal aortic aneurysm: association between haptoglobin phenotypes, elastase activity, and neutrophil count in the peripheral blood. 1156 38

Urokinase-type plasminogen activator (uPA) is increased in human abdominal aortic aneurysm (AAA). Chronic infusion of angiotensin II (Ang II) results in AAA in apolipoprotein E-deficient mice. We tested the hypothesis that Ang II infusion results in an elevation of uPA expression contributing to aneurysm formation. Ang II or vehicle was infused by osmotic pumps into apoE-KO mice. All mice treated with Ang II developed a localized expansion of the suprarenal aorta (75% increase in outer diameter), accompanied by an elevation of blood pressure (22 mmHg), compared to the vehicle-treated group. Histological examination of the dilated aortic segment revealed similarities to human AAA including focal elastin fragmentation, macrophage infiltration, and intravascular hemorrhage. Ang II treatment resulted in a 13-fold increase in the expression of uPA mRNA in the AAA segment in contrast to a twofold increase in the atherosclerotic aortic arch. Increased uPA protein was detected in the abdominal aorta as early as 10 days after Ang II infusion before significant aorta expansion. Thus, Ang II infusion results in macrophage infiltration, increased uPA activity, and aneurysm formation in the abdominal aorta of apoE-KO mice. These data are consistent with a causal role for uPA in the pathogenesis of AAA.
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PMID:Angiotensin II increases urokinase-type plasminogen activator expression and induces aneurysm in the abdominal aorta of apolipoprotein E-deficient mice. 1158 73

The hallmark feature of abdominal aortic aneurysm (AAA) is the progressive degeneration of aortic wall. Matrix proteoglycans (PGs) play important roles in the development of vascular diseases and the function of the tissue. In this study, we examined the concentration, expression and localization of the small extracellular matrix PG biglycan and decorin. The concentration of small PGs present in normal and aneurysmal aortas was determined by biochemical methods following extraction of the tissues with guanidine hydrochloride and treatment with collagenase/elastase, isolation by ion-exchange and gel chromatographies and identification by Western blotting. The levels of mRNA encoding for biglycan and decorin were evaluated in corresponding tissue samples by reverse transcriptase polymerase chain reaction (RT-PCR). Distribution of extracellular matrix macromolecules was examined using Movat's pentachrome staining and localization of biglycan and decorin by immunohistochemistry. Both normal and aneurysmal aortas contained almost equal amounts of decorin (1.13+/-0.08 and 1.22+/-0.10 mg uronic acid per g of dry defatted (dd) tissue, respectively). Furthermore, the expression of decorin was almost constant in both tissues. In normal specimens decorin accounts for 22% of total PGs, whereas in AAA ones for 60%, due to the significant loss of other matrix PGs. In contrast, the concentration of biglycan was markedly decreased in aneurysmal aortas (57%, 0.478+/-0.04 mg uronic acid per g of dd tissue) in comparison to normal ones (1.12+/-0.10 mg uronic acid per g of dd tissue). Biglycan accounts for 22% of total PGs in normal aortas and 25% of total in aneurysmal tissue. A similar decrease (60%) in the amounts of mRNA encoding for biglycan was observed in the AAA. Immunohistochemical study showed that all aortic layers of AAA were characterized by a significant loss of elastin, biglycan and other PGs/GAGs and replacement of these molecules with collagen fibrils and decorin. The obtained data suggest that the altered matrix architecture of aorta, i.e. the differential expression of biglycan and localization of decorin may well be crucial parameters accounting for the functional degeneration of the tissue and the development of aneurysmal dilatation.
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PMID:Decreased biglycan expression and differential decorin localization in human abdominal aortic aneurysms. 1241 72

Abdominal aortic aneurysm (AAA) presents itself as a progressive dilation of the abdominal aorta, leading--if untreated--to rupture. It is a common disease of the elderly, with a complex etiology. Several genetic, biochemical and environmental factors are recognized as relevant for the pathogenesis of AAA. We determined the polymorphism of the MTHFR (methylenetetrahydrofolate reductase) gene within the fourth exon (C677T) in 63 patients with AAA and compared it to that in 75 subjects of the population sample. The frequencies of the C/C, C/T and T/T genotypes were 65%, 27%, and 8% in the population sample and 33%, 60%, and 6% in the patients. This corresponds to a 4.4-fold greater risk of AAA in subjects who have the 677C/T variant of MTHFR, as compared with those who are 677C/C (p < 0.0001; 95% CI=2.11-9.34). The frequency of allele MTHFR 677T in patients (0.37) was higher than in the population sample (0.21; p < 0.007). This association between the common allele of the MTHFR gene--MTHFR 677T--and the development of AAA suggests that elevated homocysteine (Hcy) may disturb the function of the aortic wall. The disturbance may involve enhancement of elastin degradation, the process enhanced by mild hyperhomocysteinemia in minipigs. The magnitude of this effect, which refers to the AAA patients unselected for familial occurrence, indicates that the disturbance of aortic wall physiology caused by the presence of the MTHFR 677T allele is greater than the effect of the earlier described allele disequilibrium at the polymorphic alleles of the PAI1 (plasminogen activator inhibitor 1) gene seen only in familial cases of AAA.
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PMID:Increased risk of the abdominal aortic aneurysm in carriers of the MTHFR 677T allele. 1259 Jan 85

Abdominal aortic aneurysm (AAA) is associated with increased endothelin (ET-1), both systemically and locally in the aorta. Also, elastase activity is increased in human AAA, and elastase perfusion of the aorta induces aneurysm formation in animal models of AAA. However, whether elastase directly affects the ET-1-induced mechanisms of aortic smooth muscle contraction is unclear. Isometric contraction and 45Ca2+ influx were measured in aortic strips isolated from male Sprague-Dawley rats and treated with elastase (5 U/mL). To avoid degradation of the extracellular matrix proteins by elastase, experiments were performed in the presence of elastin (10 mg/mL). In normal Krebs solution (2.5 mmol/L Ca2+), ET-1 (10(-7) mol/L) caused contraction of aortic strips that was inhibited by elastase (5 U/mL). The elastase-induced inhibition of ET-1 contraction was slow in onset (4.6+/-0.4 minutes), time-dependent, complete in 34+/-3 minutes, and reversible. In Ca2+-free Krebs solution, caffeine (25 mmol/L) caused a small contraction that was not inhibited by elastase, suggesting that elastase does not inhibit Ca2+ release from the intracellular stores. Membrane depolarization by 96 mmol/L KCl, which stimulates Ca2+ entry from the extracellular space, caused a contraction that was inhibited by elastase in a concentration-dependent, time-dependent, and reversible fashion. The reversible inhibitory effects of elastase, particularly in the presence of elastin, suggest that they are not due to dissolution of the extracellular matrix or smooth muscle contractile proteins. Elastase also inhibited ET-1 and KCl-induced 45Ca2+ influx. Thus, elastase directly inhibits ET-1-induced Ca2+ entry mechanisms of vascular smooth muscle contraction, which may explain the role of elastase and ET-1 during the development of AAA.
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PMID:Elastase-induced suppression of endothelin-mediated Ca2+ entry mechanisms of vascular contraction. 1290 Apr 30

Abdominal aortic aneurysms (AAAs) occur in 5-7% of people over age 60 in the United States. Early intervention in the disease process could have a significant impact on the incidence of complications and on patient survival, but identifying incipient aneurysms can be difficult. ApoE knockout mice develop AAAs following infusion of angiotensin II (AngII) by osmotic minipump into the subcutaneous space of mice at doses ranging from 500 to 1000 ng kg(-1) min(-1) for 7-28 days. These mice are used as models of AAA development. This study tested the hypothesis that near-IR spectrometry and PCR can determine AngII dose (SEE = 26 ng kg(-1) min(-1), SEP = 37 ng kg(-1) min(-1), r2 = 0.99) and collagen/elastin (C/E) ratio (SEE = 0.38, SEP = 0.39, r2 = 0.85) in mouse aortas.
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PMID:Near-infrared spectrometry of abdominal aortic aneurysm in the ApoE-/- mouse. 1457 Feb 22

Degradation of the extracellular matrix components elastin and collagen has been implicated in vascular diseases, including abdominal aortic aneurysm (AAA) and atherosclerotic plaque rupture. Increased expression of matrix metalloproteinases (MMPs) is involved in these disease processes. Our previous studies have demonstrated that MMP-2 derived from mesenchymal cells is required for aneurysm development in a murine model. Doxycycline is a nonspecific inhibitor of MMPs. In the present study, the mechanisms of the inhibitory effects of doxycycline on MMP-2 expression from cultured human aortic smooth muscle cells (SMCs) and human aortic aneurysm tissue explants were studied. Doxycycline inhibited MMP-2 expression from cultured SMCs in a concentration-dependent manner (5-40 microg/mL; inhibitory concentration of 50%, 6.5 microg/mL). At normal therapeutic serum concentration (5 microg/mL) doxycycline significantly reduced MMP-2 production from SMCs (37%; P <.05), which were stimulated with conditioned media from macrophage or lymphocyte co-culture simulating the inflammatory milieu of AAA tissue. This correlated with a decrease in MMP-2 mRNA half-life, from 49 hours to 28 hours, which suggests that doxycycline inhibits SMC MMP-2 production in part by reducing MMP-2 mRNA stability. When AAA tissue was cultured for 10 days with doxycycline at concentrations of 2.5 to 40 microg/mL, the media exhibited a concentration-dependent decrease in both active and latent forms of MMP-2 and MMP-9. Doxycycline at a concentration of 5 microg/mL reduced active and latent MMP-2 secreted from cultured AAA tissue by 50% and 30%, respectively (P <.05). These study findings demonstrate that doxycycline at standard therapeutic serum concentrations inhibits MMP-2 expression from cultured human aortic SMCs and AAA tissue explants. Inasmuch as MMP activity contributes to extracellular matrix degradation in AAAs and atherosclerotic plaque, doxycycline may have potential value in treating these diseases.
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PMID:Mechanism of inhibition of matrix metalloproteinase-2 expression by doxycycline in human aortic smooth muscle cells. 1468 44

Many mouse models of abdominal aortic aneurysms have been developed that use a diverse array of methods for producing the disease, including genetic manipulation and chemical induction. These models could provide insight into potential mechanisms in the development of this disease. Although experimental studies on abdominal aortic aneurysms (AAAs) have used a variety of mammalian and avian approaches, there is an increasing reliance on the use of mice. The models recapitulate some facets of the human disease including medial degeneration, inflammation, thrombus formation, and rupture. Most of the mouse models of AAA are evoked either by genetically defined approaches or by chemical means. The genetic approaches are spontaneous and engineered mutations. These include defects in extracellular matrix maturation, increased degradation of elastin and collagen, aberrant cholesterol homeostasis, and enhanced production of angiotensin peptides. The chemical approaches include the intraluminal infusion of elastase, periaortic incubations of calcium chloride, and subcutaneous infusion of AngII. A common feature of these models is the reduction of AAA incidence and severity by the prophylactic administration of matrix metalloproteinase (MMP) inhibitors or genetically engineered deficiencies of specific members of this proteolytic protein family. The validation of mouse models of AAAs will provide insight into the mechanisms of progression of the human disease.
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PMID:Mouse models of abdominal aortic aneurysms. 1473 19

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