Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FACTOR XII”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources
PubMed1999

Reevaluation of the incidence of thromboembolic complications in congenital factor XII deficiency--a study on 73 subjects from 14 Swiss families.

To further elucidate the debated role of hereditary FXII deficiency as a thrombophilic risk factor this follow-up study on 65 subjects out of 12 Swiss families was undertaken (follow-up: 6 yrs). Fifteen severely FXII deficient subjects (FXII:C < 1%), 35 partially FXII deficient subjects (FXII:C > or = 1-59%), 10 with normal FXII values (FXII:C > or = 70%), and 5 non-classifiable subjects (FXII:C > or = 60-69%) were reevaluated. Eight subjects (4 severely and 3 partially FXII deficient, 1 non-classifiable) were newly enrolled. Four instances of deep vein thrombosis, one superficial vein thrombosis and one myocardial infarction were noted in 2 out of 19 severely FXII deficient subjects during a total life-time period of 866.6 patient-years. In 38 partially FXII deficient subjects (1862.8 patient-years) one ischemic cerebrovascular stroke and one superficial vein thrombosis were recorded in 2 individuals. The 10 subjects with normal FXII values (498.2 patient-years) remained thrombosis-free. One superficial vein thrombosis occurred in an unclassifiable woman. None of the 3 different FXII gene defects revealed in our patients was specifically associated with thromboembolic complications. Kaplan-Meier analysis of thrombosis-free survival suggests that hereditary partial (and probably severe) FXII deficiency does not constitute a thrombophilic condition.

Adolescent↗
PubMed1995

Molecular basis of estrogen regulation of Hageman factor XII gene expression.

Estrogen therapy has been reported to cause multiple alterations in hemostasis and to increase blood levels of several procoagulants, including Hageman factor [factor XII (FXII)]. Liver FXII gene expression has been investigated in ovariectomized rats, treated or not with 17 beta-estradiol. A 6-fold stimulation of FXII gene transcription was observed in treated compared to untreated animals, indicating that 17 beta-estradiol is able to induce FXII gene expression in vivo. We have recently shown that human FXII promoter contains an imperfect palindrome, 5'-GGGCAnnnTGACC-3', at position -43/-31 resembling the consensus estrogen-responsive element (ERE). Portions of different length of the FXII promoter were fused to the chloramphenicol acetyltransferase (CAT) coding sequence and transiently cotransfected with human estrogen receptor (ER) into NIH3T3 and HepG2 cells in the presence or absence of 17 beta-estradiol. A 230-base pair fragment of FXII promoter, spanning nucleotides - 181/49, conferred a strong estrogen responsiveness to the CAT reporter gene, suggesting that a functional ERE resides in this region. Cognate receptors, such as those for thyroid hormone or retinoic acid, did not stimulate CAT activity. Gel mobility assays demonstrated a specific interaction between ER and the 230-bp FXII promoter fragment containing the putative ERE palindrome. Similar results were obtained when an oligonucleotide spanning the consensus ERE was used; the complex between ER and FXII promoter sequences was supershifted after the addition of an anti-ER monoclonal antibody. Insertion of FXII-ERE into the heterologous thymidine kinase promoter conferred a strong estrogen responsiveness that was abolished by mutations of the 5'-half of the palindrome. These results represent the first demonstration at the molecular level of the regulation of a blood coagulation factor gene by 17 beta-estradiol as well as the first identification of a functional ERE within this class of genes.

Animals↗
PubMed2001

Homozygosity for the C-->T polymorphism at nucleotide 46 in the 5' untranslated region of the factor XII gene protects from development of acute coronary syndrome.

Recently, a C-->T polymorphism at nucleotide 46 in the 5'-untranslated region of the factor XII (FXII) gene was shown to be associated with lower levels of FXII. To study the impact of this polymorphism on the development of an acute coronary syndrome (ACS), we compared 303 patients with ACS and 227 patients with stable coronary artery disease (CAD). In the latter group, 54.2% of individuals carried wild-type FXII:46C, 37.9% were heterozygous FXII:C46T and 7.9% were homozygous for FXII:46T. In contrast, in the ACS group (n = 303), 54.1% were wild-type FXII:46C, 42.6% were heterozygous FXII:C46T and only 3.3% carried the homozygous FXII:46T genotype. The 2.5-fold lower prevalence of the FXII:46T genotype in patients with ACS could indicate a protective effect on the development of ACS (odds ratio = 0.4, 95% CI 0.1-0.9) in patients with pre-existing CAD.

5' Untranslated Regions↗
PubMed1991

Inhibition of the activation of Hageman factor (factor XII) by soluble human placental collagens types III, IV, and V.

The initial step in the formation of thrombin via the intrinsic pathway is the activation of Hageman factor (factor XII). Some, but not all, studies have shown that this activation may be brought about by collagen. We examined the effect of three types of soluble human placental collagen on Hageman factor. Collagen types III, IV, and V did not appear to activate Hageman factor under the conditions tested. To the contrary, these collagen species inhibited activation of Hageman factor by glass or ellagic acid. These studies suggest that some types of collagen may play an inhibitory role in blood coagulation.

Blood Coagulation↗
PubMed1969

Hageman factor (factor XII) deficiency in marine mammals.

Hematologic and coagulation studies were conducted on Atlantic bottlenose dolphins and killer whales. Hematologic values were similar to those in man. These animals differed from other mammals in that the Hageman factor (factor XII) was absent and this absence caused marked prolongation of coagulation. Levels of factors VIII and V were high and those of VII and X were low compared with levels in man.

Animals↗
PubMed1987

Factor XII, plasma prekallikrein, alpha 2-macroglobulin and C1-inhibitor levels in renal allograft recipients during immunosuppression with cyclosporin A--sequential measurements over four months in 17 patients.

Factor XII clotting activity (F XII), plasma prekallikrein amidolytic activity (PK), alpha 2-Macroglobulin (alpha 2-M) and C1-Inhibitor (C1-Inh) antigens have been measured in 17 patients immediately before and sequentially for up to four months after kidney transplantation. Before transplantation mean F XII and PK levels were normal (99 +/- 27% and 102 +/- 21%, respectively, mean +/- S.D.) and alpha 2-M and C1-Inh levels were slightly elevated (115 +/- 55% and 129 +/- 32%, respectively, mean +/- S.D.). In the first two weeks after transplantation a significant decrease of F XII to 65 +/- 27%, of PK to 67 +/- 20% and of alpha 2-M to 88 +/- 42%, and a rise of C1-Inh to 201 +/- 44% (mean +/- S.D.) were observed (2 p less than 0.005). F XII levels four month after operation remained significantly (2 p less than 0.05) lower than preoperatively. PK and alpha 2-M values, however, were significantly higher (2 p less than 0.05) at four months as compared to the pretransplant period. Mean F XII levels in the 17 patients at various time points after transplantation correlated positively with PK, alpha 2-M and serum albumin and negatively with CyA level and dose and serum bilirubin. PK and alpha 2-M correlated positively with each other and albumin and negatively with creatinine, bilirubin and CyA (2 p less than 0.01). Whether CyA has a direct influence on production or consumption of F XII, PK, alpha 2-M and C1-Inh, or whether the changes merely reflect altered protein metabolism awaits further study.

Adult↗
PubMed2002

Factor XII interacts with the multiprotein assembly of urokinase plasminogen activator receptor, gC1qR, and cytokeratin 1 on endothelial cell membranes.

Investigations were performed to define the factor XII (FXII) binding site(s) on cultured endothelial cells (HUVECs). Biotin- or fluorescein isothiocyanate (FITC)-FXII in the presence of 10 microM Zn(2+) specifically binds to HUVEC monolayers or cells in suspension. Collagen-stimulated platelets release sufficient Zn(2+) to support FXII binding. On laser scanning confocal microscopy or electron microscopy, FITC-FXII or Nanogold-labeled FXII, respectively, specifically bind to HUVECs. Antibodies to gC1qR, urokinase plasminogen activator receptor (uPAR) and, to a lesser extent, cytokeratin 1 (CK1) block FXII binding to HUVECs as determined by flow cytometry and soluble or solid phase binding assays. FITC-FXII on endothelial cells colocalizes with gC1qR, uPAR and, to a lesser extent, CK1 antigen. Combined recombinant soluble uPAR and CK1 inhibit 80% FITC-FXII binding to HUVECs. Peptide Y(39)HKCTHKGR(47) (YHK9) from the N-terminal region of FXII and peptide H(479)KHGHGHGKHKNKGKKNGKH(498) from HK's domain 5 cell-binding site block FITC-FXII binding to HUVECs. Peptide YHK9 also inhibits FXIIa's activation of prekallikrein and FXI on HUVECs. These combined investigations indicate that FXII through a region on its fibronectin type II domain binds to the same multiprotein receptor complex that comprises the HK binding site of HUVECs. However, plasma concentrations of HK and vitronectin inhibit FXII binding to HUVECs 100% and 50%, respectively, and plasma albumin and other proteins prevent a sufficient level of free Zn(2+) to be available to support FXII binding to HUVECs. Thus, physiologic FXII expression on HUVECs is secondary to HK binding and highly restricted in its ability to initiate prekallikrein or FXI activation.

Binding Sites↗
PubMed2002

Association of the factor XII 46C>T polymorphism with risk of coronary heart disease (CHD) in the WOSCOPS study.

AIM: To evaluate the contribution of the 46C>T polymorphism of the Factor XII (FXII) gene to risk for coronary heart disease (CHD) in the West of Scotland Coronary Prevention Study (WOSCOPS) of men with high cholesterol. BACKGROUND: WOSCOPS is a primary prevention trial that demonstrated the effectiveness of pravastatin in reducing morbidity and mortality from CHD. FXII is a protein of the contact system that plays a key role in both coagulation and fibrinolysis. Elevated activated FXII (FXIIa) levels have been previously associated with CHD. Plasma FXIIa levels are strongly determined by a 46C>T polymorphism in the FXII gene. RESULTS: 441 CHD cases and 990 controls were genotyped. The frequency of TT homozygotes was 8.3% in controls and 11.8% in cases (P=0.04). When compared with the CC+CT group (after adjustment for age, blood pressure, BMI, fibrinogen and lipid levels) the TT genotype was an independent risk factor for CHD (OR 1.48 95% CI 1.01-2.17), an effect that was only significant in the pravastatin group (OR 1.95 95% CI 1.09-3.47) and not in the placebo group (OR 1.20, 95%CI 0.72-2.02). Compared with risk in the placebo group as a whole (reference group), and after adjustment for other risk factors, men with the CC or CT genotype, but not the TT genotype showed a significant benefit from pravastatin treatment (OR, respectively, 0.61 (0.46-0.81) and 0.56 (0.40-0.79) compared with 1.10 (0.64-1.96). In a subgroup of these men, subjects with the TT genotype had, as expected, baseline levels of FXIIa that were 50% lower than those with the CC genotype, with CT subjects having intermediate levels (P<0.001 by Kruskal-Wallis test). CONCLUSIONS: The TT genotype of the FXII 46C>T polymorphism is associated with a high risk of CHD in men with high cholesterol. We hypothesise that reduced fibrinolysis in these men, as a consequence of lower plasma FXIIa, may be the mechanism leading to higher risk, and that pravastatin treatment may enhance this effect.

Case-Control Studies↗
PubMed1994

Coagulation factor XII Locarno: the functional defect is caused by the amino acid substitution Arg 353-->Pro leading to loss of a kallikrein cleavage site.

The dysfunctional coagulation factor XII (FXII) Locarno was purified from 2 L of the proposita's plasma. Studies to identify the molecular defect responsible for the lack of amidolytic and proteolytic activity of this FXII variant were performed. Amino acid sequence analysis of peptides obtained from FXII Locarno on activation with either trypsin or plasma kallikrein and dextran sulfate showed an amino acid substitution of Arg 353 by Pro. Thereby, the kallikrein cleavage site at Arg 353-Val 354 is lost. Although trypsin-activated FXII Locarno was fully cleaved at Arg 334-Asn 335 and at Arg 343-Leu 344, neither amidolytic nor proteolytic activity was generated. We conclude that proteolytic cleavage at Arg 343 in the absence of cleavage at Arg 353 is not sufficient to expose the enzymatic active site in FXII Locarno.

Amino Acid Sequence↗
PubMed1982

A study of hemostasis in ischemic cerebrovascular disease: IV. A five year follow-up of some blood coagulation parameters also including fibrinopeptide A, factor XII and prekallikrein.

Twenty-seven young adults (mean age 46) with ischemic cerebrovascular disease (ICD) were reinvestigated about 5 years after discharge and compared to 67 healthy controls. Factor VIII related antigen was again found significantly (p less than 0.005 and p less than 0.001) increased in male as well as female patients and a significant (r = 0.66, p less than 0.001) correlation was found with earlier data. Factor VIII biological activity was again found increased, significantly (p less than 0.001) in males. In contrast to earlier results antithrombin antigen and activity were significantly (p less than 0.001) decreased in males. This finding and decreased levels of factor XII in female patients (p less than 0.001) and of prekallikrein in male patients (p less than 0.01) could reflect disturbed regulatory functions or possibly constitutional differences. As in most subjects no increase of fibrinopeptide A was found, there was no sign of continuous activation of the whole coagulation sequence. Since hemostatic abnormalities were unrelated to acute phase reacting proteins they were obviously of a different nature than unspecific response to tissue damage and acute stress. High levels of factor VIII and low levels of antithrombin imply that the coagulation system could be more easily activated when other factors coincide, e.g. intimal lesions in carotide arteries.

Acute Disease↗
PubMed1993

Inhibition of the activation of hageman factor (factor XII) by eosinophils and eosinophilic constituents.

Several syndromes characterized by striking eosinophilia may be complicated by thrombosis. The experiments described indicate that, paradoxically, eosinophils and certain of their constituents inhibit the activation of Hageman factor (HF, factor XII). In earlier studies, suspensions of mixed types of granulocytes, other nucleated peripheral blood cells, and platelets inhibited activation of Hageman factor by ellagic acid, glass, and sulfatides. After these cells were sedimented by centrifugation, the supernatant fluids were also inhibitory. No attempt had been made earlier to distinguish among different granulocytic species. In the present study, suspensions of eosinophils and the supernatant fluid after eosinophils had been separated by centrifugation inhibited activation of Hageman factor by ellagic acid. The protein concentration of that amount of supernatant fluid that inhibited activation by about half was 16 micrograms/ml, approximately the same as had been described for suspensions of peripheral blood mononuclear cells. Activation of Hageman factor by ellagic acid was also inhibited by certain constituents of eosinophils, including eosinophil peroxidase, eosinophil major basic protein and eosinophil cationic protein. Inhibition was not specific for ellagic acid-induced activation of Hageman factor, as inhibition was also observed with sulfatide-induced activation. Inhibition was presumably related to neutralization of the negative charge of activators of Hageman factor. Thus, bismuth subgallate, a particulate activator of Hageman factor, was no longer effective after it had been exposed to eosinophil cationic protein. The observations reported here raise the question of whether in vivo eosinophils modulate certain of the defense reactions ascribed to Hageman factor.

Blood Proteins↗
PubMed2006

Factor XII autoantibodies as a novel marker for thrombosis and adverse obstetric history in patients with systemic lupus erythematosus.

AIM: To investigate the clinical significance of anti-factor XII (FXII) in a large cohort of patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: This study comprised 127 patients with SLE. IgG and IgM anti-FXII were tested by an in-house ELISA. 123 healthy donors comprised the control group. RESULTS: 51 (40%) patients with SLE and 9 (7%) healthy controls were positive for anti-FXII. IgG and IgM anti-FXII were frequently found in patients with thrombosis (28% and 13%, respectively). Levels of IgG and IgM anti-FXII were higher in patients with thrombosis than in the control group (p<0.001 and p=0.005, respectively). Anti-FXII was more frequent in patients with arterial thrombosis (31% vs 4% for IgG and 14% vs 3% for IgM, respectively) and venous thrombosis than in controls (37% vs 4% for IgG). IgG anti-FXII were more frequent in patients with miscarriages and fetal death (35% and 40% vs 4% for IgM). The prevalence of IgM anti-FXII was not different between groups. CONCLUSION: Anti-FXII are frequent in patients with SLE. Their presence is associated with thrombosis and adverse obstetric history, making these antibodies a novel marker for the antiphospholipid syndrome.

Abortion, Spontaneous↗
PubMed1996

Studies on factor XII in porcine plasma: purification and its conversion to activated form by porcine plasma kallikrein.

When porcine plasma was subjected to four steps of ion-exchange column chromatographies, factor XII (F. XII) was separated into two fractions, F. XII-1 and F.XII-2, and about 8.5 mg of F. XII-1 and 2.3 mg of F. XII-2 were obtained from 675 ml of the plasma. The purified proteins were found to give a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The molecular masses of F. XII-1 and XII-2 were estimated to be about 84 kDa by SDS-PAGE, and consisted of a single polypeptide chain. However, F. XII-1 converted to active form after removing Polybrene, but F. XII-2 was not activated. Activation of F. XII-2 took place on incubation with porcine plasma kallikrein, and the activation rate was increased only in the presence of negatively charged surfaces, such as sulfatide. When the preparation was incubated with sulfatide, spontaneous activation was not observed on the condition that we used. Activation of porcine F. XII-2 by porcine plasma kallikrein was found to involve the cleavage of the peptide bond on the disulfide-bridged polypeptide chain, and further fragmentation of activated form was observed during prolonged incubation time.

Amino Acids↗