fibrin and Aortic-Aneurysm--Abdominal

Imaging with the 99mTc-T2G1s monoclonal antifibrin antibody fragment (Fab') has demonstrated promise in the noninvasive detection of venous thrombi in humans. The purpose of this study was to determine whether chronic arterial thrombi can also be detected by antifibrin antibody imaging.. Eighteen subjects with chronic arterial thrombi were studied with planar and tomographic imaging at 0 to 24 hr postinjection of 99mTc-labeled T2G1s monoclonal antifibrin antibody fragment. Imaging with 111In-labeled platelets was also performed. Images were visually graded by two observers as 0, 1, 2 or 3 (no, faint, moderate or marked) uptake, and quantitative analysis of tomographic images was done in 13 subjects.. On visual analysis of planar images, 44% (8 of 18) of antifibrin patient studies were 1.0 or more and 66% (10 of 18) were judged negative compared with 94% (15 of 16) of platelet patient studies judged 1.0 or more and 6% (1 of 16) judged as negative (p < 0.01). Visual analysis of tomographic images was similar, with 61% (11 of 18) of antifibrin studies graded 1.0 or more compared with 100% (17 of 17) of platelet studies (p < 0.01). The tomographic target-to-background ratio was higher with platelets than with antifibrin antibody (2.5 +/- 1.4 versus 1.8 +/- 1.0, p < 0.05).. In the large-vessel chronic arterial thrombi studied, the results of 99mTc-labeled monoclonal T2G1s antifibrin Fab' imaging were positive in only one-half of the patients studied, significantly less than the findings with platelet imaging, which were positive in all subjects. The higher rate of positive images with labeled platelets than with labeled antifibrin antibodies may be largely due to thrombus age, with continued platelet deposition but little active fibrin deposition.

Topics: Aged; Aortic Aneurysm, Abdominal; Blood Platelets; Chronic Disease; Fibrin; Graft Occlusion, Vascular; Heart Diseases; Humans; Image Processing, Computer-Assisted; Indium Radioisotopes; Male; Radioimmunodetection; Technetium; Thrombosis

In this study, we investigated how carbonylation of fibrinogen by acrolein modified its indispensable function to enhance fibrinolysis after being converted to fibrin and contributed to generating a fibrinolysis-resistant fibrin clot. Acrolein-treated fibrinogen was subjected to tissue plasminogen activator-induced fibrinolysis assay and the effect of lysine residue carbonylation in fibrinogen on fibrinolysis was analyzed. The acrolein-treated fibrinogen-derived fibrin clot appeared more resistant to fibrinolysis and the N-acetyl 3-formyl-3,4-dehydropiperidino (FDP)-Lysine levels in the lysed solution were positively correlated with the duration of clot lysis. The lysine analog 6-amino hexanoic acid (6AHA), which mimics the C-terminal lysine of fibrin, was carbonylated and its enhancing effect on Glu

Topics: Aged; Aortic Aneurysm, Abdominal; Fibrin; Fibrinogen; Fibrinolysis; Humans; Male; Plasminogen; Thrombosis; Tissue Plasminogen Activator

The intraluminal thrombi (ILT) of abdominal aortic aneurysms (AAA) contain neutrophils, which can secrete elastase. We evaluated whether plasma neutrophil elastase-derived cross-linked fibrin degradation products (E-XDP) could reveal the presence, size and mechanical stress of AAAs and its ILTs.. E-XDP levels were elevated in patients with AAA compared with controls (. E-XDP is a marker of the presence of AAA and coexisting aneurysms as well as the volume and mechanical stress of the ILT.

Topics: Aged; Aorta; Aortic Aneurysm, Abdominal; Case-Control Studies; Fibrin; Fibrin Fibrinogen Degradation Products; Finite Element Analysis; Humans; Inflammation; Leukocyte Elastase; Male; Middle Aged; Multivariate Analysis; Retrospective Studies; Stress, Mechanical; Thrombosis

Thrombotic changes in fibrin networks contribute to increased cardiovascular risk in patients with abdominal aortic aneurysm (AAA). Given that aspirin modulates the fibrin network, we aimed to determine if aspirin therapy is associated with changes in ex-vivo fibrin clot characteristics in AAA patients and also conducted an exploratory analysis of 5-year mortality in these individuals.. We recruited 145 male patients, divided into controls (aortic diameter < 3 cm, n = 49), AAA not taking aspirin (AAA-Asp, n = 50) and AAA on 75 mg day(-1) aspirin (AAA+Asp, n = 46), matched for aneurysm size. Characteristics of clots made from plasma and plasma-purified fibrinogen were investigated using turbidimetric analysis, permeation studies, and confocal and electron microscopy. Plasma fibrinogen, D-dimer and inflammatory marker levels were also measured.. Maximum absorbance (MA) of plasma clots from controls was lower than that of AAA patients not on aspirin (AAA-Asp) at 0.30 ± 0.01 and 0.38 ± 0.02 au, respectively (P = 0.002), whereas aspirin-treated subjects had MA similar to controls (0.31 ± 0.02 P = 0.9). Plasma clot lysis time displayed an identical pattern at 482 ± 15, 597 ± 24 and 517 ± 27 s for control, AAA-Asp and AAA+Asp (P = 0.001 and P = 0.8). The lysis time of clots made from purified fibrinogen of AAA-Asp was longer than that of AAA+Asp patients (756 ± 47 and 592 ± 52 s, respectively; P = 0.041). Permeation studies and confocal and electron microscopy showed increased clot density in AAA-Asp compared with the AAA+Asp group. Mortality in AAA-Asp and AAA+Asp was similar, despite increased cardiovascular risk in the latter group, and both exhibited higher mortality than controls.. Aspirin improves fibrin clot characteristics in patients with AAA, which may have important clinical implications.

Topics: Aged; Aortic Aneurysm, Abdominal; Aspirin; Case-Control Studies; Fibrin; Fibrinolysis; Humans; Male; Middle Aged

Abdominal aortic aneurysms (AAAs) typically develop an intraluminal thrombus (ILT), yet most computational models of AAAs have focused on either the mechanics of the wall or the hemodynamics within the lesion, both in the absence of ILT. In the few cases wherein ILT has been modeled directly, as, for example, in static models that focus on the state of stress in the aortic wall and the associated rupture risk, thrombus has been modeled as an inert, homogeneous, load-bearing material. Given the biochemomechanical complexity of an ILT, there is a pressing need to consider its diverse effects on the evolving aneurysmal wall. Herein, we present the first growth and remodeling model that addresses together the biomechanics, mechanobiology, and biochemistry of thrombus-laden AAAs. Whereas it has been shown that aneurysmal enlargement in the absence of ILT depends primarily on the stiffness and turnover of fibrillar collagen, we show that the presence of a thrombus within lesions having otherwise the same initial wall composition and properties can lead to either arrest or rupture depending on the biochemical effects (e.g., release of proteases) and biomechanical properties (e.g., stiffness of fibrin) of the ILT. These computational results suggest that ILT should be accounted for when predicting the potential enlargement or rupture risk of AAAs and highlight specific needs for further experimental and computational research.

Topics: Aorta, Abdominal; Aortic Aneurysm, Abdominal; Biomechanical Phenomena; Collagenases; Fibrin; Fibrinolysin; Humans; Models, Cardiovascular; Pancreatic Elastase; Stress, Mechanical; Thrombosis

Thrombus ages, defined as four relative age phases, are related to different compositions of the intraluminal thrombus (ILT) in the abdominal aortic aneurysm (AAA) (Tong et al., 2011b). Experimental studies indicate a correlation between the relative thrombus age and the strength of the thrombus-covered wall.. On 32 AAA samples we performed peeling tests with the aim to dissect the material (i) through the ILT thickness, (ii) within the individual ILT layers and (iii) within the aneurysm wall underneath the thrombus by using two extension rates (1mm/min, 1mm/s). Histological investigations and mass fraction analysis were performed to characterize the dissected morphology, to determine the relative thrombus age, and to quantify dry weight percentages of elastin and collagen in the AAA wall.. A remarkably lower dissection energy was needed to dissect within the individual ILT layers and through the thicknesses of old thrombi. With increasing ILT age the dissection energy of the underlying intima-media composite continuously decreased and the anisotropic dissection properties for that composite vanished. The quantified dissection properties were rate dependent for both tissue types (ILT and wall). Histology showed that single fibrin fibers or smaller protein clots within the ILT generate smooth dissected surfaces during the peeling. There was a notable decrease in mass fraction of elastin within the thrombus-covered intima-media composite with ILT age, whereas no significant change was found for that of collagen.. These findings suggest that intraluminal thrombus aging leads to a higher propensity of dissection for the ILT and the intima-media composite of the aneurysmal wall.

Topics: Aged; Aged, 80 and over; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Aortic Dissection; Collagen; Elastin; Endothelium, Vascular; Fibrin; Humans; Middle Aged; Pressure; Thrombosis

Abdominal Aortic Aneurysm (AAA) involves dilatation of the abdominal aorta, with a natural history of expansion and eventual rupture. We have previously shown that AAA patients form denser clots with smaller pores, which are more resistant to fibrinolysis. The aim of this study was to use functional polymorphisms of the fibrinolytic system to identify how changes to proteins involved in fibrinolysis may play a role in the development of AAA.. Caucasian subjects ≥ 55 years (602 AAA patients and 490 matched controls) were genotyped for four polymorphisms (α-2-antiplasmin α2AP Arg6Trp and Arg407Lys, Thrombin-activatable fibrinolysis inhibitor TAFI Thr325Ile and tissue plasminogen activator tPA 7351C→T). DNA was extracted from blood, and genotype identified using real time PCR. Fibrin clot structure was analysed by permeation and turbidity in a subset of patients and controls.. Genotypes across the study population were in Hardy-Weinberg Equilibrium. The two α2AP polymorphisms, Arg6Trp and Arg407Lys were in linkage disequilibrium (P<0.0001), and possession of a 407Lys allele negatively associated with AAA (odds ratio 0.833, CI95 0.7-0.991, P=0.040). The TAFI Thr325Ile and the tPA 7351C→T polymorphisms were not associated with AAA. The α2AP 407Lys allele was not associated with in-vitro fibrinolysis times in plasma from patients with AAA.. Possession of the α2AP 407Lys allele was negatively associated with AAA, and thus changes in α2AP may affect aneurysm growth and development. These data indicate that the regulation of plasmin activity (through binding to α2AP), rather than plasmin generation (TAFI, tPA), may play a role in AAA.

Topics: Aged; alpha-2-Antiplasmin; Aortic Aneurysm, Abdominal; Case-Control Studies; Chi-Square Distribution; England; Female; Fibrin; Fibrinolysis; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Linkage Disequilibrium; Male; Middle Aged; Odds Ratio; Phenotype; Polymorphism, Single Nucleotide; Prevalence; Prospective Studies; Real-Time Polymerase Chain Reaction; Risk Factors; White People

Basing on data of analysis of the hemostasis system state in the patients, suffering abdominal aorta aneurysm, a tendency for raising of postoperative soluble fibrin and D-dimer content in the blood plasm and reduction of these indices on the third day was noted. The abovementioned markers content depends on the aneurysm size, the fibrin deposits presence, the terms from clinical signs beginning to the certain therapy administration and anticoagulants application. Information about correlation between content of D-dimer and soluble fibrin in the treatment dynamics is important for determination of activation degree in the patients blood coagulation system and the thrombotic complications prognosis.

Topics: Anticoagulants; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Blood Coagulation; Blood Coagulation Tests; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Male; Middle Aged; Prognosis; Solubility; Thrombosis

Abdominal aortic aneurysm (AAA) is characterized by widening of the aorta. Once the aneurysm exceeds 5.5 cm, there is a 10% risk of death due to rupture. AAA is also associated with mortality due to other cardiovascular disease. Our aim was to investigate clot structure in AAA and its relationship to aneurysm size.. Plasma was obtained from 49 controls, 40 patients with small AAA, and 42 patients with large AAA. Clot formation was studied by turbidity, fibrin pore structure by permeation, and time to half lysis by turbidity with tissue plasminogen activator. Plasma clot pore size showed a stepwise reduction from controls to small to large AAA. Lag phase for plasma clot formation and time to half lysis were prolonged, with smaller AAA samples showing intermediate response. Clot structure was normal in clots made with fibrinogen purified from patients compared with controls, suggesting a role for other plasma factors. Endogenous thrombin potential and turbidity using tissue factor indicated that the effects were independent of changes in thrombin generation.. Patients with AAA form denser, smaller pored plasma clots that are more resistant to fibrinolysis, and these characteristics correlate with aneurysm size. Clot structure may play a role in AAA development and concomitant cardiovascular disease.

Topics: Aged; Aortic Aneurysm, Abdominal; Case-Control Studies; Fibrin; Fibrinolysis; Humans; Male; Microscopy, Confocal; Thrombin; Thrombosis

Little is known about architecture of intraluminal thrombus (ILT) in abdominal aortic aneurysm (AAA). We present a 74-year-old woman with AAA and high cardiovascular risk. Scanning electron microscopy of ILT removed during surgery showed that its luminal layer is relatively rich in fibrin fibers forming irregular compact structure with low amounts of erythrocytes and platelets, while abluminal portion is composed of densely packed fibrin with caniculi. The structure of ILT may differ largely among AAA patients contrary to previous findings and may reveal large dense fibrin-rich areas deprived of cells, which impair fibrinolysis and stabilize the thrombus size.

Topics: Aged; Aortic Aneurysm, Abdominal; Blood Platelets; Erythrocytes; Female; Fibrin; Humans; Microscopy, Electron, Scanning; Thrombosis

An intraluminal thrombus (ILT) forms in the majority of abdominal aortic aneurysms (AAAs). While the ILT has traditionally been perceived as a byproduct of aneurysmal disease, the mechanical environment within the ILT may contribute to the degeneration of the aortic wall by affecting biological events of cells embedded within the ILT. In this study, the drained secant modulus (E(5) approximately modulus at 5% strain) of ILT specimens (luminal, medial, and abluminal) procured from elective open repair was measured and compared using unconfined compression. Five groups of fibrin-based thrombus mimics were also synthesized by mixing various combinations of fibrinogen, thrombin, and calcium. Drained secant moduli were compared to determine the effect of the components' concentrations on mimic stiffness. The stiffness of mimics was also compared to the native ILT. Preliminary data on the water content of the ILT layers and mimics was measured. It was found that the abluminal layer (E(5)=19.3kPa) is stiffer than the medial (2.49kPa) and luminal (1.54kPa) layers, both of which are statistically similar. E(5) of the mimics (0.63, 0.22, 0.23, 0.87, and 2.54kPa) is dependent on the concentration of all three components: E(5) decreases with a decrease in fibrinogen (60-20 and 20-15mg/ml) and a decrease in thrombin (3-0.3 units/ml), and E(5) increases with a decrease in calcium (0.1-0.01M). E(5) from two of the mimics were not statistically different than the medial and luminal layers of ILT. A thrombus mimic with similar biochemical components, structure, and mechanical properties as native ILT would provide an appropriate test medium for AAA mechanobiology studies.

Topics: Aged; Aged, 80 and over; Aortic Aneurysm, Abdominal; Aortic Rupture; Endothelium, Vascular; Extracellular Space; Female; Fibrin; Humans; Male; Microscopy, Electron, Scanning; Middle Aged; Molecular Mimicry; Stress, Mechanical; Thrombosis

: The presence of an abdominal aortic aneurysm (AAA) independently predicts cardiovascular disease (CVD) and its complications. Levels of plasma markers of fibrin turnover are raised in men with a large AAA (at least 5.5 cm) and predict CVD risk in healthy subjects. This study examined fibrin turnover in men with a small AAA.. : Seventy-five men with a small AAA (30-55 mm) were compared with 90 controls matched for age, sex and race. Haemostatic and fibrinolytic parameters were assessed.. : Men with a small AAA had higher mean levels of fibrinogen (2.92 versus 2.59 g/l; P = 0.019), thrombin-antithrombin (TAT) complex (4.57 versus 1.89 ng/ml; P < 0.001), prothrombin F1 + 2 (1.13 versus 0.82 ng/ml; P = 0.004) and D-dimer (346.7 versus 120.2 ng/ml; P < 0.001). All markers correlated with maximum aortic diameter determined by ultrasonography. On multivariable regression the association between presence of an AAA and fibrinogen, TAT complex, prothrombin F1 + 2 and D-dimer levels remained significant after adjustment for confounding influences.. : Fibrin turnover was increased in these men with a small AAA, independently of concomitant CVD, conventional risk factors and inflammatory markers. Enhanced fibrin turnover may contribute to the risk of cardiac complications in this group.

Topics: Aged; Antithrombin III; Aortic Aneurysm, Abdominal; Cardiovascular Diseases; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Hemostasis; Humans; Male; Peptide Hydrolases; Regression Analysis; Risk Factors

This study was conducted to clarify the effect of the direction of pressure measurement on the pressure readout in fibrinous thrombus of the abdominal aortic aneurysm.. Three weights of 468 g (weight 1), 578 g (weight 2), and 675 g (weight 3) were molded. A specimen of human fibrinous thrombus was positioned under the weights. Because the surface area of the weights and the thrombus was 400 mm(2), weights 1, 2, and 3 caused pressures of 88, 108, and 127 mm Hg, respectively. Pressure measurements were performed at different angles between the sensor and the applied force (0 degrees , 22.5 degrees , 30 degrees , 45 degrees , 60 degrees , 67.5 degrees , 90 degrees ) Thrombi of 10 different patients were analyzed. Pressure measurements in the thrombi at different angles were statistically compared by a linear mixed model analysis.. The measurements at 90 degrees differed statistically from the measurements at 0 degrees , 22.5 degrees , 30 degrees , 45 degrees , 60 degrees , and 67.5 degrees (P < .001). The pressure readout was only similar to the applied pressure when the pressure sensor was positioned at 90 degrees to the applied force. Pressure measurements in other sensor positions resulted in lower pressure measurements. Pressure changes were detected in all sensor positions. There appeared to be no significant difference between the pressure measurements taken at same angles in the 10 thrombi (P > .05).. In fibrinous thrombus of abdominal aortic aneurysm, the direction of pressure measurement influenced the pressure readout.

Topics: Aortic Aneurysm, Abdominal; Aortic Rupture; Blood Pressure; Blood Pressure Determination; Fibrin; Humans; Linear Models; Thrombosis; Transducers, Pressure

Acquired abdominal aortic aneurysms are usually associated with a mural thrombus through which blood continues to flow. Some early data suggest that aneurysmal evolution correlates with the biological activity of the thrombus. Our hypothesis was therefore that the thrombus could adsorb blood components and store, release, and participate in the activation of proteases involved in aneurysmal evolution. For this purpose, we have explored both the metalloproteinase and fibrinolytic systems in the thrombus and the wall of human aneurysms. We have first investigated blood clot formation and lysis in vitro. Spontaneous clotting induces a release of promatrix metalloproteinase (pro-MMP)-9 into the serum that was fourfold higher than in paired control plasma (P < 0.001). Fibrinolysis progressively released more MMP-9 in a time-dependent manner (P < 0.01). After selective isolation, we demonstrated that polymorphonuclear leukocytes are the main source of MMP-9 release during clot formation. Protease content was then analyzed in 35 mural thrombi and walls of human abdominal aortic aneurysms sampled during surgical repair. In 15 aneurysms, the liquid phase at the interface between the thrombus and the wall was sampled separately. Both thrombus and wall contained MMP-2 and MMP-9 but the ratio MMP-9/MMP-2 was higher in the thrombus than in the wall. The liquid interface also contained active MMP-9. Immunohistochemistry of the thrombus confirmed these findings, showing the presence of polymorphonuclear leukocytes at the luminal pole of the thrombus, co-localizing with MMP-9 storage. In contrast, MMP-3 and MMP-7 were only present in the aneurysmal wall. Plasminogen was present in the mural thrombus but plasmin activity was present in both thrombus and wall. In the liquid interface, plasmin-alpha(2)-anti-plasmin complexes were detected demonstrating in vivo the activation of plasminogen. In contrast, u-PA and t-PA were detectable only in the wall, suggesting that plasminogen present in the thrombus could be activated by factors secreted by the arterial wall. This was demonstrated in vitro, in which co-incubation of thrombus and wall extracts generated plasmin in the presence of a fibrin matrix and activated MMPs. In conclusion, our study strongly suggests that the mural thrombus, by trapping polymorphonuclear leukocytes and adsorbing plasma components could act as a source of proteases in aneurysms that may play a critical role in enlargement and rupture.

Topics: Abdominal Wall; Aortic Aneurysm, Abdominal; Blood Coagulation; Endopeptidases; Enzyme Activation; Fibrin; Fibrinolysin; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 3; Matrix Metalloproteinase 7; Matrix Metalloproteinase 9; Neutrophils; Plasminogen; Thrombosis; Tissue Inhibitor of Metalloproteinases; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

Accurate estimation of the wall stress distribution in an abdominal aortic aneurysm (AAA) may prove clinically useful by predicting when a particular aneurysm will rupture. Appropriate constitutive models for both the wall and the intraluminal thrombus (ILT) found in most AAA are necessary for this task. The purpose of this work was to determine the mechanical properties of ILT within AAA and to derive a more suitable constitutive model for this material. Uniaxial tensile testing was carried out on 50 specimens, including 14 longitudinally oriented and 14 circumferentially oriented specimens from the luminal region of the ILT, and 11 longitudinally oriented and 11 circumferentially oriented specimens from the medial region. A two-parameter, large-strain, hyperelastic constitutive model was developed and used to fit the uniaxial tensile testing data for determination of the material parameters. Maximum stiffness and strength were also determined from the data for each specimen. Scanning electron microscopy (SEM) was conducted to study the regional microstructural difference. Our results indicate that the microstructure of ILT differs between the luminal, medial, and abluminal regions, with the luminal region stronger and stiffer than the medial region. In all cases, the constitutive model fit the experimental data very well (R2>0.98). No significant difference was found for either of the two material parameters between longitudinal and circumferential directions, but a significant difference in material parameters, stiffness, and strength between the laminal and medial regions was determined (p<0.01). Therefore, our results suggest that ILT is an inhomogeneous and possibly isotropic material. The two-parameter, hyperelastic, isotropic, incompressible material model derived here for ILT can be easily incorporated into finite element models for simulation of wall stress distribution in AAA.

Topics: Aged; Analysis of Variance; Aortic Aneurysm, Abdominal; Aortic Dissection; Elasticity; Endothelium; Fibrin; Humans; In Vitro Techniques; Microscopy, Electron, Scanning; Models, Cardiovascular; Regression Analysis; Stress, Mechanical; Tensile Strength; Thrombosis

does open surgery for abdominal aortic aneurysm (AAA) influence coagulation?. in 23 patients operated on for AAA, cubital blood was sampled pre-, intra- and postoperatively. Femoral blood was also sampled intraoperatively.. preoperatively, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and soluble fibrin (SF) were elevated in AAA patients. During aortic clamping all parameters increased significantly in cubital blood (p<0.01) as well as in femoral blood (p<0.001) and after aortic declamping F1+2 and TAT increased further. F1+2, TAT and SF were significantly higher in femoral than cubital blood. Postoperatively F1+2 and TAT returned to preoperative values, while SF still had a significantly higher level than preoperatively (p<0.001). Blood loss showed co-variation with F1+2 increase in femoral blood after aortic declamping (p<0.05).. these data indicate that the coagulation system was strongly activated by the occurrence of an AAA. During AAA surgery a further extensive activation was seen. The activity was still high, but on decline, one week postoperatively. Ischaemia and reperfusion of the lower part of the body were the major stimuli for thrombin generation and activity.

Topics: Adult; Aged; Antithrombins; Aortic Aneurysm, Abdominal; Fibrin; Humans; Ischemia; Male; Middle Aged; Peptide Fragments; Protein Precursors; Prothrombin; Reperfusion; Thrombin

A pathologic feature commonly associated with abdominal aortic aneurysms is the presence of variably sized and shaped intraluminal thrombus, which may be fundamental to the disease process. However, the precise role of the intraluminal thrombus in the formation, enlargement, and rupture of abdominal aortic aneurysms is unknown. The hypothesis tested in this study was whether there were structural features of aortic thrombi to suggest that it may be involved in the pathogenesis of abdominal aortic aneurysms. We have investigated this hypothesis using a variety of structural and biochemical techniques.. Tests performed were light, transmission, and scanning electron microscopy; fluid permeability measurements; and Western blots.. Intraluminal thrombus found in abdominal aortic aneurysms is structurally complex and is traversed from the luminal to abluminal surface by a continuous network of interconnected canaliculi. Quantitative microscopic analysis of the thrombus shows cellular penetration for at least 1 cm from the luminal surface of the thrombus. Macro-molecular penetration may be unrestricted throughout the entire thickness of the thrombus. Fibrin deposition occurred throughout the thrombus, whereas fibrin degradation occurred principally at the abluminal surface.. These principally structural studies support the hypothesis that the thrombus is a self-sustaining entity that may have significance in the pathophysiologic mechanism of abdominal aortic aneurysms.

Topics: Aorta, Abdominal; Aortic Aneurysm, Abdominal; Blood Cells; Blotting, Western; Female; Fibrin; Fibrinolysis; Humans; Immunohistochemistry; Male; Microscopy, Electron; Microscopy, Electron, Scanning; Permeability; Thrombosis

Aortic aneurysms are characterized by the destruction of the extracellular matrix of the media, whereas occlusive disease involves excess matrix accumulation within the intima. Plasmin degrades extracellular matrix directly and indirectly by activation of latent metalloenzymes. To determine the expression of tissue- and urokinase-type plasminogen activators, immunoassay, fibrin autography, Northern analysis, and immunohistochemistry were performed on specimens of aneurysmal (n = 12), occlusive (n = 8), and healthy (n = 6) aorta.. Immunoassay of tissue-type plasminogen activator revealed 8.7 +/- 0.9 ng tissue-type plasminogen activator/mg extracted protein in aneurysmal aorta, 5.7 +/- 0.3 ng/mg in normal aorta, and 2.5 +/- 0.3 ng/mg in occlusive aorta (p < 0.05 for comparisons between all groups). No urokinase-type plasminogen activator antigen was detected by urokinase-type plasminogen activator immunoassay. Fibrin autography exhibited lytic activity at 64 kDa and 54 kDa attributable to tissue-type plasminogen activator and urokinase-type plasminogen activator. The vast majority of fibrinolysis was secondary to free tissue-type plasminogen activator and was greatest in aneurysmal disease and least in occlusive disease. There was only a small amount of lysis secondary to urokinase-type plasminogen activator. Expression of tissue-type plasminogen activator and urokinase-type plasminogen activators mRNA was comparable in aneurysmal and occlusive aortas. In contrast to occlusive disease, aneurysms had an inflammatory cell infiltrate characterized by the expression of urokinase-type plasminogen activator by specific mononuclear cells. Tissue-type plasminogen activator expression was evident in the intima of normal and diseased aorta and in the media of diseased aorta.. Differential expression of plasminogen activators within the arterial wall may contribute to the unique pathogenesis of aneurysmal and occlusive aortic disease.

Topics: Adult; Aged; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Aortic Diseases; Arterial Occlusive Diseases; Autoradiography; Blotting, Northern; DNA Probes; Electrophoresis, Polyacrylamide Gel; Fibrin; Humans; Immunohistochemistry; Middle Aged; Plasminogen Activators