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At least 991 records · Page 55Linked to original sources
PubMed2005

A novel variant fibrinogen, deletion of Bbeta111Ser in coiled-coil region, affecting fibrin lateral aggregation.

BACKGROUND: Functional fibrinogen concentration of a male infant showed <0.50 g/l and we speculated this patient as a dysfibrinogenemia or hypofibrinogenemia. METHODS: We analyzed propositus and his parent by DNA sequencing and by thrombin-catalyzed fibrin polymerization for purified plasma fibrinogen. RESULTS: Although functional fibrinogen determinations based on Clauss method showed the marked discrepancy of values among 3 sets of reagent and analyzer, we found a novel heterozygous variant fibrinogen, Kyoto IV, caused by 3-bp deletion in Bbeta-chain gene corresponding to the deletion of 111Ser located in coiled-coil region. We suggested that the discrepancy of fibrinogen values among 3 assays was caused by the difference in NaCl concentration in reagents for determination and analyzed the polymerization under the conditions of various NaCl concentrations. Although under normal physiological conditions Kyoto IV fibrinogen augmented the polymerization as compared with normal control, in 0.21 mol/l NaCl Kyoto IV fibrinogen showed abruptly impaired polymerization curve compared with normal control. CONCLUSION: Variant fibrinogen, BbetaDelta111Ser, showed augmented lateral aggregation under normal physiological conditions and the residue located in coiled-coil region, Bbeta111Ser, plays an important role in the lateral aggregation.

Adult↗
PubMed2005

In situ conformational analysis of fibrinogen adsorbed on Si surfaces.

Fibrinogen is a major plasma protein. Previous investigations of structural changes of fibrinogen due to adsorption are mostly based on indirect evidence after its desorption, whereas our measurements were performed on fibrinogen in its adsorbed state. Specific enzyme-linked immunosorption experiments showed that the amount of adsorbed fibrinogen increased as the surface became more hydrophobic. Atomic force microscopy (AFM) investigations revealed the trinodular shape of fibrinogen molecules adsorbed on hydrophilic surfaces, whereas all of the molecules appeared globular on hydrophobic surfaces. The distribution of secondary structures in adsorbed fibrinogen was quantified by in situ Fourier-transform infrared (FTIR) analysis. Substrates of identical chemical bulk composition but different surface hydrophobicity permit direct comparison among them. Adsorption properties of fibrinogen are different for each degree of hydrophobicity. Although there is some increase of turn structure and decrease of beta-sheet structure, the secondary structure of adsorbed fibrinogen on hydrophilic surface turned out to be rather similar to that of the protein in solution phase with a major alpha-helix content. Hydrophilic surfaces exhibit superior blood compatibility as required for medical applications.

Adsorption↗
PubMed2005

Adsorption of fibrinogen on tantalum oxide, titanium oxide and gold studied by the QCM-D technique.

The adsorption of human fibrinogen on tantalum oxide, titanium oxide and gold surfaces has been studied by quartz crystal microbalance with dissipation (QCM-D) at 37 degrees C. Two different protein concentrations have been used, one close to physiological concentration (1 mg/ml) and one significantly lower (0.033 mg/ml). To further characterize the adsorbed fibrinogen layer, the subsequent binding of both polyclonal and monoclonal antibodies of fibrinogen is studied. We found that the viscoelastic properties of the fibrinogen layer depends strongly on the initial protein concentration. The trend is generally seen for all three surfaces. The fibrinogen layer on gold and tantalum oxide is found to have the same viscoelastic properties, which are different from those found for the fibrinogen layer adsorbed on titanium oxide. The dependency of the surface chemistry on the viscoelastic properties of the fibrinogen layer is observed directly for the 0.033 mg/ml solution, and indirectly through the antibody response for the 1 mg/ml solution. From this we conclude that the orientation and/or denaturation of fibrinogen on a surface depends on the surface chemistry and the protein concentration in the solution, and that the binding of antibodies is a useful way to detect this difference.

Adsorption↗
PubMed2006

Protein concentration and adsorption time effects on fibrinogen adsorption at heparinized silica interfaces.

Heparin was modified with adipic dihydrazide and covalently linked to surface-activated silica wafers. X-ray photoelectron spectroscopy was used at each stage of derivatization and showed that successful immobilization had taken place. Surfaces were imaged with atomic force microscopy to determine the uniformity of the heparin layer as well as its thickness. In situ ellipsometry was used to estimate layer thickness as well, and to study protein concentration and adsorption time effects on the adsorption and elution kinetics exhibited by human plasma fibrinogen. The adsorbed amount of fibrinogen increased with time and concentration on each type of surface. Under all experimental conditions, fibrinogen adsorbed at a lower rate and to a lower extent on heparinized as compared to unheparinized silica. In addition, buffer elution experiments showed that fibrinogen was less tightly bound to heparinized silica. In order to examine behavior relative to fibrinogen mobility at these interfaces, the sequential adsorption of fibrinogen was recorded. The difference in adsorption rates between the first and second adsorption cycles, evaluated at identical mass density, indicated that post-adsorptive molecular rearrangements had taken place. In general, higher solution concentration and longer adsorption time in the first adsorption step led to more rearrangement, and these history dependent effects were more pronounced on the heparinized silica. These rearrangements are suggested to involve clustering of adsorbed fibrinogen, in this way increasing the amount of unoccupied area at the interface. These rearrangements were presumably facilitated on the heparinized silica by enhanced lateral mobility of fibrinogen at this negatively charged, highly hydrophilic interface.

Adipates↗
PubMed2006

Plasma fibrinogen and serum C-reactive protein are associated with non-small cell lung cancer.

OBJECTIVES: There is an association between coagulation and lung cancer. Therefore, pre-operative plasma fibrinogen and serum C-reactive protein (CRP) concentration were assessed to determine their association with tumour characteristics and to ascertain any role in patient selection for curative resection. METHODS: These parameters were compared with tumour size, pTNM stage, and possibility of complete resection in 93 patients with non-small cell lung cancer who underwent surgical resection. RESULTS: Plasma fibrinogen concentration (r(s)=0.34, P=0.001) and serum CRP concentration (r(s)=0.34, P=0.001) were positively correlated with maximum pathological tumour size. A higher plasma fibrinogen concentration was associated with squamous cell carcinoma versus adenocarcinoma (4.5+/-0.13 g/L versus 3.6+/-0.28 g/L; P=0.008), with a trend towards a similar association for CRP (P=0.06). Pathological T stage was also associated with mean plasma fibrinogen and serum CRP concentration (P=0.01 and 0.04, respectively), but pN stage was not associated with either parameter. Incomplete resection occurred in 23% of patients with plasma fibrinogen > 5 g/L or serum CRP > 40 mg/L (versus only 8% when fibrinogen < or = 5 g/L and CRP < or = 40 mg/L; P=0.09). CONCLUSIONS: Plasma fibrinogen and serum CRP are associated with tumour characteristics. High values were associated with inability to achieve complete resection which may refine patient selection for thoracotomy when used with other staging modalities. Attempted resection may be justified in a patient of borderline fitness who has favourable plasma fibrinogen and serum CRP concentration, where a high resection rate is possible. As the relationship was with T stage rather than N stage it may be complimentary to PET scanning, which has only marginally better accuracy for T stage than CT scanning.

Adenocarcinoma↗
PubMed2005

The K469E polymorphism of the intercellular adhesion molecule-1 gene is associated with plasma fibrinogen level in type 2 diabetes.

Intercellular adhesion molecule-1 (ICAM-1) is involved in inflammation and development of atherosclerotic change of vascular endothelium. The aim of the present study is to investigate whether K469E polymorphism of the ICAM-1 gene is associated with various clinical factors including plasma fibrinogen in patients with type 2 diabetes. ICAM-1 gene polymorphism was examined using polymerase chain reaction and restriction enzyme analysis in 360 type 2 diabetic patients. Plasma fibrinogen levels and other clinical variables were measured as well as circulating soluble ICAM-1 (sICAM-1) levels by enzyme-linked immunosorbent assay. The distribution of ICAM-1 genotypes, EE, EK, and KK, was not significantly different between type 2 diabetes and 152 healthy control subjects. Among 3 groups according to ICAM-1 genotypes in type 2 diabetes, no difference was found in adiposity, glycemic control, lipid profile, insulin sensitivity evaluated by homeostasis model assessment, or sICAM-1. Regarding fibrinogen, the patients with E allele showed significantly lower plasma fibrinogen levels in a dose-dependent manner (P = .033). Spearman rank correlation analyses revealed that ICAM-1 genotype showed significant correlation with plasma fibrinogen level (P < .001). In multiple regression analysis, ICAM-1 genotype was independent contribution factor of plasma fibrinogen level as well as high-density lipoprotein-cholesterol and urinary albumin excretion (R2 = 0.148, P < .001). In conclusion, K469E polymorphism of the ICAM-1 gene had impact on plasma fibrinogen level independently of other clinical factors in 360 type 2 diabetic patients, suggesting that fibrinogen is a candidate which links the ICAM-1 gene polymorphism to atherosclerosis.

Albuminuria↗
PubMedDate not supplied

Blood low shear rate rheometry: influence of fibrinogen level and hematocrit on slip and migrational effects.

Red blood cell (RBC) aggregation is of prime importance in vivo and in vitro for low flow rates. It may be estimated by rheometrical measurements at low shear rates, but these are perturbed by slip and migrational effects which have already been highlighted in the past. These effects lead to a torque decay with time so that the true value of the stress at low shear rates may be greatly underestimated. Elevated aggregation being associated with different diseases, pathological blood samples show more pronounced perturbing effects and a strong time dependency in low shear rate rheometry. To test the dependence of slip and migrational effects on RBC aggregation, and particularly to determine the way in which they depend upon fibrinogen concentration ([Fb]), a home-made measuring system with roughened internal and external walls (170 microns roughness) was used to study low shear rate rheometry for RBC suspensions in PBS buffer containing albumin (at 50 g/l) and fibrinogen at various concentrations. The influences of hematocrit, shear rate, and fibrinogen concentration were investigated. Particular attention was paid to data acquisition at low shear rates (10(-3) s-1 to 3 x 10(-2) s-1). The combined influence of hematocrit and fibrinogen was investigated by adjusting hematocrit to 44 or 57% and fibrinogen concentration ([Fb]) to 3.0-4.5-6.5 g/l. Microscopic observations of the blood samples at rest were performed. They showed that different structures were formed according to fibrinogen concentration. The rheometrical measurements indicated that torque decay with shearing duration was strongly dependent on fibrinogen concentration and on shear rate at fixed hematocrit. Migrational and slip effects were more pronounced as shear rate decreased, fibrinogen concentration was raised, and hematocrit was lowered. The results have been explained on the basis of the expected microstructure of flowing blood in relation to the microscopic observations at rest.

Erythrocyte Aggregation↗
PubMed2001

Variability in fibrinogen measurements: an obstacle to cardiovascular risk stratification.

The clinical utility of fibrinogen measurement has been limited by large intraindividual variability. Several approaches that have been shown to improve the repeatability of fibrinogen include acquisition of samples at the same time of day, standardized sample procurement techniques, and multiple replicate sampling. This study employed established pre-analytical and analytical techniques known to reduce fibrinogen variability, including the acquisition of three replicate samples, each analyzed in duplicate, to evaluate the impact of intraindividual variability in fibrinogen measurement at baseline and 3 months on cardiovascular risk in 60 healthy subjects. Classification accuracy was evaluated by the ability to categorize subjects into tertiles of fibrinogen. Only 55% (33/60) of the subjects were correctly assigned to the appropriate fibrinogen tertile. Fibrinogen measurements varied by more than 10% in 45% of subjects and by 5% in 80% of subjects. Intraindividual variability in fibrinogen measurement with a functional assay limits cardiovascular risk assessment even when three replicates are averaged.

Adult↗
PubMed2000

Relationships between fibrinogen and insulin resistance.

A relationship between plasma fibrinogen levels and insulinemia, as well as the different parameters of the insulin resistance syndrome has been described. The aim of the present paper was to investigate whether plasma fibrinogen concentrations were linked to plasma insulin levels or to the degree of insulin resistance. For this purpose, 62 nondiabetic, nonhypertensive patients, 30 men and 32 women, with body mass indexes (BMIs) and ages ranging from 18.6 to 50.2 kg/m(2) and from 19 to 60 years, respectively, were studied. Insulin sensitivity was quantified by the minimal model procedure over a 180-min intravenous glucose tolerance test with iterative sampling. Plasma insulin was determined by radioimmunoassay without cross-reactivity to human proinsulin, and fibrinogen by the method of Clauss. Insulin sensitivity ranged from 0.009 to 23.2 min(-1)/(microU/ml)x10(-4), covering the whole range of insulin sensitivities. Fibrinogen ranged from 1.70 to 5.07 g/l. There was a significant negative correlation between fibrinogen and insulin sensitivity (r=-0.76,P<0.0001) and a positive correlation between fibrinogen and basal insulin (r=0.56,P<0.0001). After adjustment for BMI, body fat mass and waist-to-hip ratio, these two relationships remained significant. In addition, a multiple regression analysis was performed to assess the independent effect of the following related variables: fibrinogen, insulin sensitivity, insulinemia and BMI. Only insulin sensitivity appeared to account for the ability to predict fibrinogen values. Thus, we hypothesized it was likely that the state of insulin resistance rather than hyperinsulinemia per se was related to hyperfibrinogenemia. We proposed an interpretation of these data in connection with some factors like free fatty acids or tumor necrosis factor-alpha, which have been implicated in the pathogenesis of insulin resistance. Nevertheless, prospective and intervention studies are needed to assess whether there is a simple association or a causal relationship between insulin resistance and hyperfibrinogenemia.

Adult↗
PubMed1996

Multiple peaks induced by domain-specific binding of fibrinogen in anion-exchange high-performance liquid chromatography.

A domain binding model was developed for explaining the multiple peak chromatograms obtained in the high-performance liquid chromatography of pure fibrinogen on a DEAE polymethacrylate column using different gradients of ammonium chloride. The different peaks for fibrinogen result from the binding of either the D or E domain of fibrinogen to the packing material. This was confirmed by comparing the retention times of the chromatograms for fibrinogen, fragment D1 and fragment E. Native and denatured forms of fibrinogen are proposed to be important to fibrinogen's interaction with the column, hiding or exposing the E domain, respectively. Different gradient speeds resolve a different number of peaks for fibrinogen, with slow gradients yielding essentially one peak and fast gradients 10 or more peaks. Temperature studies were done to confirm the model. Different commercial sources of fibrinogen showed different proportions of native and denatured/degraded forms.

Chromatography, High Pressure Liquid↗
PubMed1997

Hemorheologic profiles of plasma fibrinogen and blood viscosity from silent to acute and chronic cerebral infarctions.

Hemorheologic changes from silent to acute and chronic cerebral infarction have seldom been reported. We evaluated hemorheologic profiles of the whole blood viscosity, plasma viscosity and fibrinogen level in stroke at-risk patients with silent cerebral infarction, patients with acute or chronic cerebral lacunar infarction, and subjects at low risk for stroke. Hemorheologic profiles were measured in 88 subjects: (1) 36 patients with silent cerebral infarction (mean 64.7 years), who provided no clinical history of having had definitive stroke but showing > 5 mm lesions of cerebral infarction or periventricular hyperintensity (PVH) observed in magnetic resonance imaging (MRI) T2-weighted images; (2) 12 patients with acute cerebral lacunar infarction (mean 69.1 years), measured within 3 days and repeated 1 month after onset; (3) 25 patients with chronic cerebral lacunar infarction (mean 66.2 years), measured 12.5 months after onset; and (4) 15 subjects at low risk for stroke (mean 65.8 years) without cardiovascular risk factors or lesions on MRI. Patients with silent cerebral infarction were subdivided into two groups of less advanced and more advanced grades, based on the number of infarctions or the grade of PVH. Whole blood viscosity (shear rates: 22.5-225.0 s-1), corrected blood viscosity for 45% standard hematocrit (Hct), plasma viscosity, fibrinogen, serum total protein, albumin, and Hct were measured. Plasma fibrinogen levels were lower in silent cerebral infarctions than in chronic cerebral infarctions (P < 0.01), and patients with more advanced grades of silent cerebral infarction showed higher levels of plasma fibrinogen than those with less advanced grades (P < 0.01 and P < 0.05). Whole blood viscosity, corrected blood viscosity (Hct 45%), plasma viscosity and fibrinogen levels in acute cerebral infarction within 3 days after onset were higher significantly than those in subjects at low risk for stroke. Plasma fibrinogen level persisted to be elevated up to 1 month after onset, which continued as well in patients with chronic cerebral infarction. Advanced grades of silent cerebral infarction in stroke at-risk patients are accompanied by elevations of plasma fibrinogen level, which increases further after onset of cerebral infarction; such abnormalities persist up to the chronic stage. Elevated plasma fibrinogen level might reflect progression of atherogenesis in patients with advanced grades of silent cerebral infarction, resulted in an increased probability as to be a risk factor for cerebral infarction.

Acute Disease↗
PubMed2003

[Seasonal variation in plasma fibrinogen in dipper and non-dipper patients with mild-moderate essential hypertension].

BACKGROUND AND OBJECTIVE: Increased plasma fibrinogen is recognized as a significant parameter for assessing the potential risk of myocardial infarction and stroke. A seasonal variation has been reported for plasma fibrinogen, with highest values occurring in the coldest months of the year. On the other hand, the lack of nocturnal decline in blood pressure has been associated with an increase in cardiovascular events. Accordingly, we have quantified the yearly variation in plasma fibrinogen in hypertensive patients classified according to their nocturnal decline in blood pressure. PATIENTS AND METHOD: We studied 577 mild-to-moderate hypertensive patients (254 men), 53.8 13.8 years of age. Blood pressure was measured every 20 min during the day and every 30 min at night for 48 consecutive hours. Physical activity was simultaneously evaluated at 1-min intervals with a wrist actigraph. A complete blood test was performed on the same day before starting blood pressure monitoring. The circannual variation of plasma fibrinogen was established for all patients as well as for subgroups of dippers (n = 287) and non-dippers (n = 290; patients with a nocturnal blood pressure decline < 10% of the diurnal mean) by multiple-component analysis. RESULTS: For the whole group of hypertensive patients, plasma fibrinogen was characterized by a highly significant seasonal variation (p < 0.001), with a mean value of 324 mg/dl, double circannual amplitude (i.e, extent of predictable change along the year) of 75 mg/dl, and time of peak value on the first week of March. This circannual variation can be best represented by a model that includes components with periods of 12 and 6 months. The same model also characterized dippers as well as non-dippers, analyzed separately. Non-dippers showed higher plasma fibrinogen throughout the whole year as compared to dippers (p = 0.002). CONCLUSIONS: The elevation of plasma fibrinogen in non-dipper patients as compared to dippers could support the association between the lack of nocturnal decline in blood pressure with an increase in cardiovascular events, since the circannual variation in fibrinogen is timely correlated with the reported yearly variation in coronary events.

Adult↗
PubMed2000

Relationship between lipid peroxidation and plasma fibrinogen in middle-aged men.

The relationship between lipid peroxidation (plasma malondialdehyde [MDA] concentration) and plasma fibrinogen level was analyzed in 144 men, aged 53-62 years. MDA was measured colorimetrically and fibrinogen with the thrombin method. Mean plasma MDA concentration was 12.6 (SD 1.2) micromol/L, plasma fibrinogen level 2.91 (0.47) g/L, and body mass index 27.1 (3.5) kg/m(2). Prevalence of smoking was 17%. MDA correlated moderately with fibrinogen. Both MDA and fibrinogen correlated positively with waist hip ratio (WHR) and blood leukocyte count, but inversely with VO(2)max. Both MDA and fibrinogen levels were higher in smokers than in non-smokers (p<0. 01). In multiple stepwise regression analysis, plasma MDA, VO(2)max, smoking, and leukocyte count explained 38.1% of the variance in plasma fibrinogen level, with the individual contributions reaching 20.6%, 9.7%, 5.5%, and 2.3%, respectively. WHR, serum triglycerides, and age did not enter the model. These data suggest that increased lipid peroxidation is associated with elevated plasma fibrinogen level in middle-aged men.

Arteriosclerosis↗
PubMed2000

Discrepancy between fibrinogen concentrations determined by clotting rate and clottability assays during the acute-phase reaction.

Assays based on clotting rate are commonly used as a routine method for determining the fibrinogen concentration in plasma. However, little is known about the influence of the acute-phase reaction on this assay. In order to disclose discrepancies between the fibrinogen concentrations obtained by a clotting rate assay (as described by Clauss) and a reference assay for total clottable protein (according to Jacobsson), we compared the fibrinogen concentrations determined by these two methods in plasma-samples collected preoperatively and on postoperative days 1, 3, and 5 in patients undergoing major elective surgery. The HMW (High Molecular Weight)-, LMW- and LMW'-fibrinogen fractions of the patient samples were also determined. In preoperative samples, good agreement between the two assays was found. In samples collected on postoperative days 1 and 3, the fibrinogen concentrations measured with the clotting rate assay were significantly higher than the concentrations measured with the total clottable protein assay (p=0.015 on both days). SDS-gel electrophoresis showed an increase in the median HMW-fraction from 69.7% (range 64.3-70.4) in preoperative samples to 85.8% (80.7-87.6) in samples drawn on day 3. The difference between fibrinogen concentrations obtained by the two methods was significantly correlated to the HMW-fraction of the samples. We conclude that during an acute-phase reaction, fibrinogen concentrations obtained by a clotting rate assay (as described by Clauss) are significantly higher than those measured by a total clottable protein assay (according to Jacobsson). The difference between the two methods correlates well with the relative HMW-fraction, indicating that the increase in HMW-fibrinogen is the main contributor to the observed discrepancy.

Acute-Phase Reaction↗
PubMed2005

Fibrinogen and fibrin.

Fibrinogen is a large, complex, fibrous glycoprotein with three pairs of polypeptide chains linked together by 29 disulfide bonds. It is 45 nm in length, with globular domains at each end and in the middle connected by alpha-helical coiled-coil rods. Both strongly and weakly bound calcium ions are important for maintenance of fibrinogen's structure and functions. The fibrinopeptides, which are in the central region, are cleaved by thrombin to convert soluble fibrinogen to insoluble fibrin polymer, via intermolecular interactions of the "knobs" exposed by fibrinopeptide removal with "holes" always exposed at the ends of the molecules. Fibrin monomers polymerize via these specific and tightly controlled binding interactions to make half-staggered oligomers that lengthen into protofibrils. The protofibrils aggregate laterally to make fibers, which then branch to yield a three-dimensional network-the fibrin clot-essential for hemostasis. X-ray crystallographic structures of portions of fibrinogen have provided some details on how these interactions occur. Finally, the transglutaminase, Factor XIIIa, covalently binds specific glutamine residues in one fibrin molecule to lysine residues in another via isopeptide bonds, stabilizing the clot against mechanical, chemical, and proteolytic insults. The gene regulation of fibrinogen synthesis and its assembly into multichain complexes proceed via a series of well-defined steps. Alternate splicing of two of the chains yields common variant molecular isoforms. The mechanical properties of clots, which can be quite variable, are essential to fibrin's functions in hemostasis and wound healing. The fibrinolytic system, with the zymogen plasminogen binding to fibrin together with tissue-type plasminogen activator to promote activation to the active enzyme plasmin, results in digestion of fibrin at specific lysine residues. Fibrin(ogen) also specifically binds a variety of other proteins, including fibronectin, albumin, thrombospondin, von Willebrand factor, fibulin, fibroblast growth factor-2, vascular endothelial growth factor, and interleukin-1. Studies of naturally occurring dysfibrinogenemias and variant molecules have increased our understanding of fibrinogen's functions. Fibrinogen binds to activated alphaIIbbeta3 integrin on the platelet surface, forming bridges responsible for platelet aggregation in hemostasis, and also has important adhesive and inflammatory functions through specific interactions with other cells. Fibrinogen-like domains originated early in evolution, and it is likely that their specific and tightly controlled intermolecular interactions are involved in other aspects of cellular function and developmental biology.

Animals↗
PubMed1986

Biochemical properties of fibrinogen binding protein (clumping factor) of the staphylococcal cell surface.

The staphylococcal fibrinogen binding protein of a strain of coagulase-negative Staphylococcus aureus was purified 229 fold in terms of the haemagglutination unit compared to the starting material by affinity chromatography on fibrinogen-Sepharose. By polyacrylamide gel electrophoresis in both reduced and unreduced gels, the protein showed one major band and minor bands with relative molecular masses of 62,000, 61,000, and 59,000, respectively. The isoelectric point was between 10.2 and 10.8 determined by isoelectric focusing in polyacrylamide gel. By the agar diffusion test one band was obtained against anti-whole cell rabbit serum. Amino acid analysis of fibrinogen binding protein showed glycine, glutamic acid, lysine, alanine, aspartic acid, and arginine as the major components. Protein A or teichoic acid extracted from the homologous strain did not show fibrinogen binding activity assayed by haemagglutination and anti-fibrinogen binding activity of anti-whole cell Fab. The amount of the fibrinogen binding protein to absorb the activity of anti-whole cell Fab was decreased to 1/60 of that of the starting material. Sheep red blood cells coated with the fibrinogen binding protein agglutinated in 0.001% (w/v) fibrinogen solution.

Amino Acids↗
PubMed2003

Fibrinogen predicts ischaemic stroke and advanced atherosclerosis but not echolucent, rupture-prone carotid plaques: the Copenhagen City Heart Study.

AIMS: Whether the association between fibrinogen and cardiovascular events reflects an association with advanced atherosclerosis in general, or rupture-prone plaques in particular, is unclear. We examined whether fibrinogen predicts incidence of ischaemic stroke, advanced atherosclerosis (measured as carotid artery stenosis) and/or echolucent, rupture-prone plaques. METHODS AND RESULTS: Study 1-8755 Copenhagen City Heart Study stroke-free participants; we observed 235 ischaemic strokes during 6 years of follow-up. Study 2-318 carotid stenosis patients and 1584 age- and gender-matched controls. Study 3-159 patients with echolucent vs 159 patients with echo-rich carotid artery plaques. Fibrinogen above vs below the median value of 3 g l(-1)predicted risk of ischaemic stroke (relative risk: 1.9; 95% CI: 1.4-2.5; 235 events). Significant risk was found in men (2.7; 1.7-4.2; 113 events) and with a similar trend in women (1.4; 0.9-2.0; 122 events), in young (5.2; 1.1-26; eight events) and middle aged (2.9; 1.6-5.4; 64 events) with a similar trend in the elderly (1.4; 1.0-2.0; 163 events). Fibrinogen levels in those with and without ischaemic stroke were 3.6 and 3.1 g l(-1)(ANCOVA: P<0.0001). Likewise, in those with and without carotid artery stenosis fibrinogen levels were 4.7 and 3.1 g l(-1)(P<0.0001); equivalent values for high-sensitive C-reactive protein were 3.6 and 1.4 mg l(-1)(P<0.0001). Finally, neither fibrinogen nor high-sensitive C-reactive protein levels differed between those with echolucent and echo-rich carotid artery plaques (P=0.61 and P=0.28); the power to exclude a 15% increase in fibrinogen or a 50% increase in high-sensitive C-reactive protein was 98 and 54%, respectively. CONCLUSIONS: Elevated fibrinogen predicts future ischaemic strokes, particularly in men and in the young and middle aged. This is most likely a reflection of advanced atherosclerosis, rather than an association with rupture-prone plaques.

Adult↗
PubMed1997

Metal-ion catalyzed oxidation affects fibrinogen activity on platelet aggregation and adhesion.

Exposure of fibrinogen to the Fe3+/ascorbate oxidative system resulted in structural modifications and altered functionality of the glycoprotein. The overnight treatment of fibrinogen by oxidants caused a 20-fold increase of carbonyl content with respect to the native protein. Formation of dityrosines as well as loss of tryptophan following fibrinogen oxidation were observed. The occurrence of conformational changes of the fibrinogen molecule as a consequence of the oxidative treatment was also established. Oxidized fibrinogen showed a distinct capability from the native molecule to mediate platelet aggregation and adhesion. The percentage of ADP-induced platelet aggregation decreased as a function of fibrinogen oxidative damage. Further, both unstimulated platelets and ADP-activated platelets showed a reduced ability to adhere to oxidized fibrinogen than to the native protein. These results suggest that oxidative treatment alters fibrinogen domains involved in the recognition and the binding of this molecule by the platelet receptor GP IIb/IIIa.

Ascorbic Acid↗