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At least 127 records · Page 7Linked to original sources
PubMed1998

-455G/A polymorphism of the beta-fibrinogen gene is associated with the progression of coronary atherosclerosis in symptomatic men: proposed role for an acute-phase reaction pattern of fibrinogen. REGRESS group.

Increased plasma fibrinogen levels have been identified as a risk indicator for myocardial infarction, stroke, and thrombosis. Both environmental and genetic factors make an important contribution to plasma fibrinogen levels in humans. In the present study we evaluated, in patients with serum cholesterol levels between 4 and 8 mmol/L, the relation of plasma levels and polymorphisms of fibrinogen with coronary artery disease (CAD), cross-sectionally at baseline and after a 2-year follow-up period in which they received either a placebo or pravastatin. Higher plasma fibrinogen levels (3.9 g/L) were observed at baseline in patients with the -455AA genotype than in patients with the -455GA (3.2 g/L) and -455GG (3.1 g/L) genotypes of the -455G/A fibrinogen beta gene polymorphism (P<.05). Plasma levels of fibrinogen were not related to the baseline angiographic variables (mean segment diameter [MSD] and minimum obstruction diameter [MOD]), nor to the quantitative changes in these angiographic variables. However, in the placebo group, patients with the -455AA genotype had more progression of CAD, expressed by a significantly greater decrease of the MSD and MOD, after the 2-year follow-up period than patients with the other genotypes. The -455G/A polymorphism was related to the progression of CAD, and pravastatin therapy seemed to offset this deleterious effect. We hypothesized that the -455A allele may promote a stronger acute-phase response in fibrinogen and that the resulting higher fibrinogen levels may form the pathogenetic basis for the stronger progression of coronary atherosclerosis. Experiments to verify this hypothesis are being proposed and advocated, in view of the possibility of identifying a genetic marker that can recognize a subgroup of patients with an increased risk who may benefit from early treatment with lipid-lowering or anticoagulant drugs.

Aged↗
PubMed1972

Fibrinogen St. Louis: a new inherited fibrinogen variant, coincidentally associated with hemophilia A.

A patient with classical hemophilia (factor VIII deficiency) was found to have a new abnormal fibrinogen (fibrinogen St. Louis). Other family members exhibited either defect alone. Fibrinogen St. Louis was inherited as an autosomal dominant and was not associated with clinical bleeding. When compared with normal fibrinogen, fibrinogen St. Louis was found to have defective fibrin polymerization and possibly a slower release of fibrinopeptides. The prolonged thrombin times were partially corrected by calcium chloride and protamine sulfate. Ultracentrifugal sedimentation, electrophoretic mobility, DEAE chromatographic pattern, carbohydrate content, N-terminal amino acids, immunodiffusion, and immunoelectrophoretic patterns and electrophoresis of reduced and alkylated fragments were all normal. In contrast to fibrinogen St. Louis, the most similar other fibrinogen variant (fibrinogen Zurich) was found to be heterogeneous by several criteria and to have reduced hexose content.

Adult↗
PubMed1995

The effects of pH on the generation of turbidity and elasticity associated with fibrinogen-fibrin conversion by thrombin are remarkably influenced by sialic acid in fibrinogen.

In fibrinogen-fibrin conversion by thrombin, the polymerization of a fibrin monomer is accompanied by gelation and an increase turbidity. Since sialic acids at the terminal of the carbohydrate chains bound to fibrinogen are part of the low affinity calcium binding site necessary for polymerization, they are closely involved in the network structure of fibrin clots. Fibrin clots derived from asialofibrinogen exhibited definite differences in turbidity and elasticity compared with those derived from intact fibrinogen, and were markedly dependent on the pH during the reaction. The turbidity during polymerization of fibrin, evaluated according to the absorbance at 350 nm, was maximum at pH 6.5-7.0, but it decreased in the other pH ranges, with the changes being unremarkable at higher pH levels but remarkable at lower pH ranges. The turbidity of fibrin derived from asialofibrinogen was far higher than that from intact fibrinogen near neutrality, but decreased rapidly and was lower than in intact fibrinogen at higher and lower pH ranges. Concerning the elasticity evaluated by thromboelastography, the coagulation time (k) and the maximum amplitude (ma) were lower in asialofibrinogen, indicating a deterioration of the clotting function of fibrinogen with the loss of sialic acid. These results suggest that sialic acid bound to fibrinogen is closely related to the fibrin network formation in blood coagulation, which is the most important function of fibrinogen, and plays a functional role in the stabilization of fibrin clot formation against environmental changes, including pH.

Asialoglycoproteins↗
PubMed1996

Beta-fibrinogen gene-455 G/A polymorphism and fibrinogen levels. Risk factors for coronary artery disease in subjects with NIDDM.

OBJECTIVE: To investigate the association of a G/A polymorphism at position -455 of the beta-fibrinogen gene and fibrinogen levels in the development of coronary artery disease (CAD) in subjects with NIDDM. RESEARCH DESIGN AND METHODS: In 187 Caucasian subjects with NIDDM, presence of CAD was taken as a clinical history of angina, myocardial infarction, coronary angioplasty, or coronary artery bypass grafting, confirmed from medical case notes. RESULTS: Fibrinogen levels were significantly higher in subjects with CAD (n = 38, 3.41 [3.12-3.73] g/l) than those without (n = 149, 2.99 [2.87-3.11] g/l, P = 0.004 [geometric mean, 95% CI]). Comparing the genotype frequencies by chi 2 testing, there was a significant difference between subjects with CAD (GG = 0.84, GA + AA = 0.16) and those without (GG = 0.64, GA + AA = 0.36, P = 0.02). In a logistic regression model, including age, BMI, cholesterol, sex, smoking, triglycerides, and plasminogen activator inhibitor antigen as covariates, genotype and fibrinogen levels were significantly associated with CAD. The odds ratio for having CAD in individuals homozygous for the G allele compared with those possessing the A allele was 1.77 (1.08-2.90), P = 0.03; and for an increase of 1 g/l in fibrinogen levels was 1.60 (1.00-2.60), P = 0.05. CONCLUSIONS: These data suggest a relationship between the -455 G/A beta-fibrinogen gene polymorphism and the development of CAD in subjects with NIDDM. This relationship was not associated with variations in fibrinogen levels, suggesting that this polymorphism may be in linkage with a polymorphism within the coding region of the beta-fibrinogen gene, which results in an alteration in the stability of the fibrin clot.

Adenine↗
PubMed2001

A hamster antibody to the mouse fibrinogen gamma chain inhibits platelet-fibrinogen interactions and FXIIIa-mediated fibrin cross-linking, and facilitates thrombolysis.

Murine models employing genetically altered mice have the potential to provide important new information about the hemostatic system, but before such data can be extrapolated to humans it is necessary to define the similarities and differences between murine and human hemostasis. After establishing the similarities of murine fibrinogen to human fibrinogen in its pattern of proteolysis in response to plasmin and its cross-linking by factor XIIIa, we studied a new hamster monoclonal antibody (mAb) 7E9 that reacts with the gamma chain of mouse fibrinogen. This antibody inhibits platelet adhesion to fibrinogen, platelet-mediated clot retraction, platelet aggregation, and FXIIIa-mediated cross-linking of fibrin; it also facilitates tissue plasminogen activator (tPA)-mediated lysis of fibrin formed either in the absence or presence of platelets. These data provide evidence that the C-terminus of mouse fibrinogen gamma chain, like that of human fibrinogen, is involved in fibrinogen binding to platelets and FXIIIa-mediated cross-linking of fibrin. Our data raise the possibility that a therapeutic agent that targets the C-terminus of the gamma chain in human fibrinogen might have broad antithrombotic and profibrinolytic effects.

Animals↗
PubMed2000

[beta-fibrinogen gene -455A/G polymorphism and plasma fibrinogen level in Chinese stroke patients].

OBJECTIVE: To explore the relationship between beta-fibrinogen gene -455A/G polymorphism and plasma fibrinogen level and to determine the influence of the mutation on ischaemic stroke. METHODS: Ninety-one patients (63.5 +/- 10.1 years) with ischaemic stroke, 74 control patients (60.6 +/- 10.8 years) without any thromboembolic events and 98 healthy blood donors (37.5 +/- 13.3 years) were enrolled in this trial. beta-fibrinogen gene -455A/G polymorphism was analyzed from all subjects by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) with restrictive enzyme Hae III. Plasma fibrinogen levels were obtained from prothrombin time (PT) assay. The parameters were compared between any two different groups by unpaired t-test and Chi-square test. Before the analysis, log transformation was carried out for concentrations of fibrinogen. RESULTS: Frequency of H2 allele was higher in male patients with ischaemic stroke than in control patients (22.7% vs 7.1%, chi(2) = 5.56, P < 0.02). There was no significant difference in female patients. In the subjects without any thromboembolic events (including control patients and healthy blood donors), frequency of H2 decreased with age (>/= 40, 21.3%; 41 approximately 59, 15.4%; >/= 60, 10.0%). Among male control patients and healthy blood donors, the level of plasma fibrinogen was lower in the H1H1 genotype (287 g/L +/- 96 g/L and 234 g/L +/- 58 g/L) than in H1H2 and H2H2 genotypes (331 g/L +/- 44 g/L and 307 g/L +/- 55 g/L; t = 2.53 and 9.67, P < 0.05); among females, this tendency was not found. CONCLUSION: Plasma fibrinogen expression is affected by the beta-fibrinogen gene - 455A/G polymorphism. H2 allele is a risk factor for ischaemic stroke in Chinese men.

Adult↗
PubMed2002

The effect of fibrinogen genotype on fibrinogen levels after strenuous physical exercise.

We have examined the effect of two beta-fibrinogen gene promoter polymorphisms (-455G>A and -854G>A) on the fibrinogen response to severe exercise in a group of male army recruits undergoing basic training. Fibrinogen was measured pre-training and again serially after severe 48 h final military exercise (FME). Out of 884 subjects, 762 completed training of whom 250 were selected for post-FME study. Fibrinogen levels (g/l) were significantly elevated over baseline levels 2, 48 and 96 h after FME, representing increases of 15.7%, 3.4% and 7.6% (p <0.005; p = 0.05 and p <0.005 respectively), with higher levels in -455A allele carriers than genotype -455GG: 3.17+/-0.05 vs. 2.94+/-0.05 (p <0.001), 2.86+/-0.05 vs. 2.60+/-0.05 (p <0.0005) and 2.98+/-0.06 vs. 2.69+/-0.06 (p <0.0005) at 2, 48 and 96 h respectively. There was no effect of the -854G>A polymorphism on fibrinogen, even after taking into account beta-fibrinogen -455 genotype. Thus the fibrinogen -455G>A polymorphism influences fibrinogen levels following exercise. The effect of genotype might be clinically relevant at times of hyperfibrinogenaemia such as following an acute inflammatory response.

Acute-Phase Reaction↗
PubMed2002

beta-fibrinogen gene -455A/G polymorphism and plasma fibrinogen level in Chinese stroke patients.

OBJECTIVES: To investigate the relationship between the beta-fibrinogen gene -455A/G polymorphism and plasma fibrinogen level and to determine the influence of the mutation on ischemic stroke. METHODS: Ninety-one patients (63.5 +/- 10.1 years) with ischemic stroke and 74 elderly control subjects (60.6 +/- 10.8 years) without any thromboembolic events and 98 healthy blood donators as young control (37.5 +/- 13.3 years) were enrolled in this trial. The beta-fibrinogen gene -455A/G polymorphism was analyzed for all subjects by PCR-RFLP with the restrictive enzyme Hae III, while plasma fibrinogen levels were obtained from the prothrombin time (PT) assay. For statistical analysis, the parameters were compared between any two different groups by the unpaired Student's t test and the Chi-square test. Before analysis, log transformations for concentrations of fibrinogen were carried out. RESULTS: H2 allele frequency was higher in male ischemic stroke patients than in the elderly control (22.7% vs 7.1%, chi(2) = 5.56, P < 0.02). There was no significant difference between the female groups. In those patients without any thromboembolic events (both elderly and young control groups), the frequency of H2 decreased with age (< or = 40, 21.3%; 41 - 59, 15.4%; and > or = 60, 10.2%). In the male elderly and young control groups, the level of plasma fibrinogen was lower in the H1H1 genotype (287 +/- 96 mg/dl and 234 +/- 58 mg/dl) than in H1H2 and H2H2 (331 +/- 44 mg/dl and 307 +/- 55 mg/dl; t = 2.53 and 9.67, P < 0.05). In the female elderly groups, this tendency was not found. CONCLUSION: Plasma fibrinogen expression is affected by the beta-fibrinogen gene -455A/G polymorphism, and the H2 allele may be a risk factor for ischemic stroke in Chinese males.

Aged↗
PubMed1992

Human fibrinogen heterogeneity: the COOH-terminal residues of defective A alpha chains of fibrinogen II.

Fibrinogen fraction I (340 kDa) and fraction II (305 kDa) were isolated by glycine precipitation. The subunit chains of the two fractions were separated, after reduction, by reverse-phase high performance liquid chromatography. The amino acid compositions of the B beta and tau chains of fibrinogen II were identical with those of fibrinogen I. In contrast, the A alpha chains of fibrinogen II were composed of two populations, one comprising homogeneous, intact A alpha chains and the other consisting of heterogeneous, deficient A alpha chains (A alpha' chains) of lengths varying according to the sizes of their COOH-terminal defects. The molar ratio of the A alpha to the A alpha' chains in fibrinogen II was 1.16:1. The amino acid composition and sequence analyses of the TPCK-trypsin peptides derived from the A alpha' chains revealed that the COOH-terminal residues of the A alpha' chains were mainly Asn-269, Gly-297 and Pro-309. These results indicate that the fibrinogen II molecule is asymmetrical and can be represented by the formula (A alpha) (A alpha')(B beta)2(tau)2 and that fibrinogen II cannot be a plasmin degradation product of fibrinogen I.

Amino Acid Sequence↗
PubMed2004

Beta-fibrinogen promoter -455 G/A (HaeIII) polymorphism prediction of plasma fibrinogen but not of ischemic cerebrovascular disease.

OBJECTIVE: The -455 G/A (HaeIII) polymorphism of beta-fibrinogen gene influences levels of plasma fibrinogen. We further investigated whether it influences the risk of ischemic cerebrovascular disease. METHODS: We accumulated 134 acute ischemic cerebrovascular disease (ICVD) cases and compared their -455 G/A status with a control group (n = 166). The beta-fibrinogen gene -455 G/A polymorphism was analyzed for all subjects by PCR-RFLP with the restrictive enzyme HaeIII. RESULTS: Plasma fibrinogen was higher in AA homozygous participants (341 mg/dL) than in participants carrying the G allele: GA (290 mg/dL), GG (298 mg/dL) in the control group. Plasma fibrinogen was also higher in AA homozygous patients (353 mg/dL) than in cases carrying the G allele: GA (287 mg/dL), GG (302 mg/dL) in the ICVD group. However, there was no significant association between beta-fibrinogen gene -455 G/A polymorphism and ICVD group. CONCLUSIONS: Although a small effect cannot be excluded, beta-fibrinogen gene -455 G/A polymorphism is an independent predictor of plasma fibrinogen, but not of ischemic cerebrovascular disease.

Alleles↗
PubMed1991

Variation in the promoter region of the beta fibrinogen gene is associated with plasma fibrinogen levels in smokers and non-smokers.

We investigated the association between fibrinogen levels and a HaeIII restriction fragment length polymorphism located at -453 bp from the start of transcription of the beta fibrinogen gene. 292 healthy men aged 45 to 69 years, recruited from general practices throughout Britain, were studied. None had a history of ischaemic heart disease. 41.1% (120) were smokers and fibrinogen levels were higher in this group. The frequency of the non-cutting allele (designated H2) was 0.19 and was the same in smokers and non-smokers. The H2 allele was associated with elevated levels of fibrinogen in both smokers and non-smokers and the effect of genotype was similar in both groups. After smoking, HaeIII genotype was the strongest predictor of fibrinogen levels and explained 3.1% of the variance in fibrinogen levels. These results confirm earlier studies that variation at the fibrinogen locus contributes to the between-individual differences in plasma fibrinogen level.

Base Sequence↗
PubMed1989

Epinephrine induces platelet fibrinogen receptor expression, fibrinogen binding, and aggregation in whole blood in the absence of other excitatory agonists.

The exposure of fibrinogen receptors is an early event in agonist-induced platelet activation. Previous measurements of fibrinogen binding or aggregation in platelet-rich plasma or washed platelets have failed to define whether the initial response to epinephrine results solely from a direct effect of this agonist. To address this problem, we have measured fibrinogen receptor exposure on platelets in whole blood by using flow cytometry and a fluorescein isothiocyanate-labeled monoclonal antibody specific for the activated fibrinogen receptor (FITC-PAC1). We also measured platelet-bound fibrinogen with an antifibrinogen monoclonal antibody (FITC-9F9) as well as platelet aggregation in whole blood. In blood anticoagulated with citrate and in the presence of a cyclooxygenase inhibitor, epinephrine (0.1 to 100 mumol/L) caused significant FITC-PAC1 binding (P less than .001) that was maximal at 10 mumol/L epinephrine. The maximal epinephrine response was one third of that observed with 10 mumol/L adenosine diphosphate (ADP) and was eliminated by yohimbine, an alpha 2-adrenergic antagonist. Incubation of the blood with apyrase or phosphoenolpyruvate plus pyruvate kinase to remove extracellular ADP resulted in a 40% to 50% reduction in the epinephrine response. Despite this, FITC-PAC1 binding was still significant at epinephrine greater than or equal to 1 mumol/L (P less than .05). No reduction in epinephrine-induced FITC-PAC1 binding was observed in the presence of ATP alpha S, an ADP receptor antagonist; cinanserin, a serotonin antagonist; or WEB-2086, a platelet activating factor antagonist. Furthermore, addition of the thrombin inhibitors hirudin or leupeptin to citrated blood had no effect on the extent of the epinephrine response. Blood anticoagulated with hirudin also demonstrated an epinephrine response, even in the presence of apyrase. Similar results were obtained when FITC-9F9 was used to detect fibrinogen binding or when aggregation was assessed by a decrease in the number of single platelets. We conclude that epinephrine itself can induce fibrinogen receptor exposure, fibrinogen binding, and aggregation. This primary response is independent of synergistic interaction of epinephrine with traces of ADP, serotonin, platelet activating factor, or thrombin. However, such synergistic interaction with ADP present in whole blood may enhance the responses induced by epinephrine.

Adenosine Diphosphate↗
PubMed1979

[The behaviour of fibrinogen and fibrinogen degradation products in myocardial infarction. Justification of a prognostic index (author's transl)].

The behaviour of fibrinogen and fibrinogen degradation products in 52 patients with myocardial infarction was analyzed with the aim of finding an evolutive prognostic index for these patients. According to the clinical course the patients who developed complications were separated from those who did not develop them; a special distinction was made of those complications classified as being of thromboembolic type. In the same way those patients who died were analyzed differentially from those who did not. When these facts were related to the behaviour of fibrinogen and of fibrinogen degradation products the following facts were observed: 1) There was an increase of fibrinogen which reached its maximum on the 5th and 6th days and which returned to normal limits on approximately the 9th day. The greatest increase was reached in those patients who developed thromboembolic complications, although the study did not allow to establish significant differences between this group and the rest of the cases. A reactive and nonspecific behaviour was suggested. 2) Fibrinogen degradation productes reached its maximum increase during the 48 hours after the myocardial infarction, without significant differences between both groups. Therefore it does not seem that a prognostic and evolutive assessment can be derived from the study of the changes in the fibrinogen time and fibrinogen degradation products in patients with myocardial infarction.

Adult↗
PubMed1978

Studies of fibrinogen metabolism in healthy and hypertensive female subjects with the use of autologous I-125-fibrinogen.

10 healthy female subjects and 15 female patients with essential hypertension were studied with respect to fibrinogen metabolism in a steady state. Autologous I-125-labeled fibrinogen (I-125-fibrinogen) was used as a tracer. Comparison of the results showed that plasma volume, t1/2 of plasma I-125-fibrinogen and fractional catabolic rate (j3p) of plasma fibrinogen (x) were not appreciably different in both groups of subjects, but plasma fibrinogen concentration, x and catabolic flux of x (j3px) (synthesis rate) were significantly higher in hypertensive subjects, whereas extravascular fibrinogen (y) and fractional transcapillary transferrate (j1) of x were significantly decreased in the patients. Further analyses of the data in both groups showed that there were significant correlations between diastolic blood pressure (P) and j1 with a regression equation of 41 = e-0.0285P, between x and j1 with a regression equation of x = 226e-0.939j 1 and between y and j1 with a regression equation of y = 12.6e0.624j 1. These results indicate that the observed decrease of j1 triggered the transition from normal to pathological steady state and is responsible for the altered metabolism and distribution of fibrinogen in hypertensive subjects.

Adult↗
PubMed1994

Freeze-dried fibrinogen or fibrinogen in EDTA stimulate the tissue-type plasminogen activator-catalysed conversion of plasminogen to plasmin.

Both soluble and insoluble fibrin stimulate the tissue-type plasminogen activator-catalysed conversion of plasminogen to plasmin. Whether fibrinogen can exert a similar effect has been a controversial issue. The present investigation shows that while fibrinogen purified by beta-alanine precipitation does not stimulate the tissue-type plasminogen activator-catalysed plasminogen activation, fibrinogen which has been either lyophilized or stripped of bound Ca2+ ions by EDTA chelation, stimulates this reaction. The data indicate that such procedures alter the molecular conformation of fibrinogen, and expose stimulatory sites which are hidden in the native fibrinogen molecule. These results may explain previous findings concerning the capacity of fibrinogen as a stimulator of the tissue-type plasminogen activator-catalysed plasminogen activation. Since even slight alteration of the molecular structure of fibrinogen leads to an increase in the tissue-type plasminogen activator stimulation, the authors suggest that this can be used to test if the fibrinogen is in a native state.

Amino Acid Sequence↗
PubMed1994

Fibrinogen plasma levels as a marker of thrombin activation: new insights on the role of fibrinogen as a cardiovascular risk factor.

Fibrinogen has recently emerged as a major risk factor for atherothrombosis. However, the pathophysiologic mechanism linking high fibrinogen concentration to cardiovascular disease is unclear. In this study 136 subjects (75 males, 61 females, age 51.7 +/- 14.4 years, mean +/- standard deviation, range 17-82) were tested for total and HDL-cholesterol, total triglycerides, apolipoprotein AI, apolipoprotein B, fibrinogen, prothrombin fragment and D-dimer. Moreover, 5 subjects who had hyperfibrinogenemia (range 450 to 950 mg/dl) for at least 6 months by repeated measurements, were treated with a short 7-day course of heparin 12,500 U/day subcutaneously. The effect of heparin on all the above mentioned parameters was observed at the end of treatment and after 7 days of wash-out. Simple regression analysis detected a positive correlation between fibrinogen and age, prothrombin fragment and D-dimer, and a negative correlation between fibrinogen and HDL-cholesterol and apolipoprotein AI. A direct correlation between age and both prothrombin fragment and D-dimer was also demonstrated. Multivariate analysis showed a persistent correlation between fibrinogen and prothrombin fragment, D-dimer and age, that was not influenced by sex, smoking habit and body mass index. In the 5 hyperfibrinogenemic subjects, heparin administration significantly reduced fibrinogen (625.4 +/- 211.1 vs 455.2 +/- 112.3 mg/dl, p < 0.03), prothrombin fragment (0.97 +/- 0.1 vs 0.63 +/- 0.2 nM, p < 0.002) and D-dimer (336 +/- 101.8 vs 275.2 +/- 78.5 ng/ml, p < 0.03). All these parameters returned to baseline after 7 days of wash-out (fibrinogen 632.5 +/- 198.2 mg/dl, prothrombin fragment 0.96 +/- 0.2 nM, D-dimer 325.8 +/- 98.65 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Evidence for two functionally different fibrinogen receptors on hemopoietic cells: the glycoprotein IIb-IIIa and the mitogenic fibrinogen receptor.

We have previously established that the mitogenic effect of fibrinogen on hemopoietic cell lines Raji and JM is mediated via a specific receptor (Levesque, J.-P. et al.: Proc. Natl. Acad. Sci. USA 83:6494-6498, 1986). In this study, we have further characterized the fibrinogen domain involved in the binding to the mitogenic receptor. This binding was not inhibited either by a monoclonal antibody against the C-terminal sequence of the fibrinogen gamma chains or by synthetic peptides containing the Arg-Gly-Asp sequence. Such inhibition is specific of the platelet fibrinogen receptor, the glycoprotein IIb-IIIa complex. Fragments containing the fibrinogen D domain were the only plasmin degradation products of fibrinogen which were mitogenic. These fragments acted via direct binding on the mitogenic receptor with a Kd of 2.24 X 10(-6) M. This value was similar to the KI value of unlabeled fragments D (2.47 X 10(-6) M). Our results suggest the presence of two different functional types of fibrinogen receptors: the glycoprotein IIb-IIIa receptor responsible both for platelet aggregation and leukocyte adhesion and killing, and the mitogenic receptor involved in proliferation control of hemopoietic cells.

Antibodies, Monoclonal↗
PubMed1989

Stimulation of fibrinogen synthesis in cultured rat hepatocytes by fibrinogen degradation product fragment D.

The direct stimulation of fibrinogen biosynthesis by fibrinogen degradation produces (FDPs) was studied in rat hepatocyte cultures. Pure rat FDP fragment D (FDP-D) (Mr 90,000) and FDP fragment E (FDP-E) (Mr 40,000) and mixtures of the two (FDP-DE) were added to rat hepatocytes cultured in serum-free hormonally defined medium. Hydrocortisone (20 microM) significantly increased synthesis of fibrinogen, as determined by incorporation of [35S]methionine. FDP-D and FDP-E did not increase fibrinogen synthesis in the presence of hydrocortisone. However, hepatocytes cultured without hydrocortisone displayed increased fibrinogen synthesis (2.0- to 2.8-fold) with FDP-D (2.6-6.7 microM) but not with FDP-E (5.7 microM). At these FDP concentrations the synthesis of albumin, haptoglobin, and transferrin was not increased. FDP-D-induced fibrinogen synthesis was inhibited (greater than 90%) by actinomycin D and cycloheximide, indicating that the increase in [35S]methionine incorporation was from de novo protein synthesis. The role of FDP-D was further substantiated by showing that FDP-D, but not FDP-E, bound to the hepatocytes. These data indicate that FDP-D, but not FDP-E, directly and specifically stimulates fibrinogen synthesis in rat hepatocytes; this stimulation does not require any additional serum or protein cofactors.

Animals↗