Monocyte Tissue Factor Expression Is Enhanced in Women who Smoke and Use Oral Contraceptives

1999 ◽  
Vol 82 (12) ◽  
pp. 1614-1620 ◽  
Author(s):  
Helma-Meta Terhalle ◽  
Ute Zakel ◽  
Ulrich Maus ◽  
Behnoush Parviz ◽  
Harald Tillmanns ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Oral Contraceptives ◽  
Transcriptional Activation ◽  
Contraceptive Use ◽  
Coagulation Cascade ◽  
Blood Monocytes ◽  
Inhibitor Molecule ◽  
Increased Risk ◽  
Menopausal Women ◽  
Tf Gene

SummaryThe association between use of oral contraceptives (OCs) and increased risk of thromboembolic disease has been firmly established. This risk increases when use of OCs is combined with cigarette smoking. The cellular mechanism favoring an hypercoagulable state under these behaviours is not known. Circulating monocytes are potent activators of the coagulation cascade through their ability to synthesize procoagulant tissue factor (TF). In the present study we report that monocyte TF expression is increased in women who use OCs and smoke.We studied monocyte TF expression in 4 groups of healthy pre-menopausal women (n = 15 each): (1) non-smoking OC non-users, (2) nonsmoking current OC users, (3) smoking OC non-users and (4) smoking OC users. TF expression was assessed on both mRNA and protein levels in unstimulated and LPS-stimulated cells. Transcriptional activation of the TF gene was assessed by analysis of the transcription factor NF-κB and its inhibitor molecule IκBα. Monocyte TF generation was significantly higher in OC users than in women who did not use OCs. Enhanced monocyte TF generation was also observed in smoking women when compared to non-smokers. Strongest monocyte TF expression occurred in women with combined smoking and use of OCs. The enhanced TF expression in monocytes from women using OCs or smoking was based on an increased TF gene transcription following activation of NF-κB. Experiments on cultured monocytes/macrophages demonstrated enhanced IκBα degradation in the presence of estradiol, suggesting that a direct hormone effect is responsible for the observed increase in monocyte TF expression.This study demonstrates that use of OCs and smoking is associated with an increase in monocyte TF expression in pre-menopausal women. Aberrant TF expression by blood monocytes may favour intravascular clotting activation in women with OC therapy. The further enhancement of TF activity observed in women who smoke and use OCs may explain the synergistic effect of smoking on risk of thromboembolic events associated with contraceptive use.

scholarly journals The risk of breast, cervical, endometrial and ovarian cancer in oral contraceptive users

2010 ◽  
Vol 63 (9-10) ◽  
pp. 657-661 ◽  
Author(s):  
Milena Veljkovic ◽  
Slavimir Veljkovic
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cervical Cancer ◽  
Oral Contraceptive ◽  
Oral Contraceptives ◽  
Young Women ◽  
Contraceptive Use ◽  
Epidemiologic Studies ◽  
Oral Contraceptive Use ◽  
Increased Risk

Introduction. Oral contraceptives, mainly combined monophasic pills, are widely used by young women who expect their physicians to prescribe them safe drugs which will not harm their health and which will simplify their life. Numerous epidemiologic studies have been performed to determine the relation between oral contraceptive use and the development of neoplasms. Breast cancer. An increased incidence of breast cancer has occurred simultaneously with the growing use of oral contraceptives. The possibility of a link between the oral contraceptive use and breast cancer has led to intensive research, but studies have provided inconsistent results causing confusion among clinicians. It was noticed that the risk of breast cancer was slightly elevated in current and recent young oral contraceptives users. That finding could be influenced by a detection bias or could be due to the biologic effect of the pills. The absolute number of additional breast cancer cases will be very small because of low baseline incidence of the disease in young women. Oral contraceptives probably promote growth of the already existing cancer, they are probably promoters not initiators of breast cancer. The available data do not provide a conclusive answer that is need. Cervical cancer. Numerous factors may influence the development of cervical cancer. The evidence suggests that current and recent oral contraceptive users have an increased risk of cervical cancer which decline after discontinuation of the application of medication. Oral contraceptives might increase the biological vulnerability of the cervix. Cervical cancer develops slowly over a long time period and can be effectively prevented by periodic cervical screening. Fortunately, oral contraceptives do not mask abnormal cervical citology. Conclusions regarding invasive cervical cancer and oral contraceptive use are not definitive but if there is any increased risk, it is low. Endometrial cancer. In oral contraceptive users the endometrium is almost under the influence of progestin component which suppresses endometrial mitotic activity and its proliferation. Most epidemiologic studies show that oral contraceptives reduce the risk of endometrial cancer and that this protective effect exists many years after the discontinuation of medication. Ovarian cancer. It has been long known that the oral contraceptive use causes protective an ovulation and reduces the risk of ovarian cancer. This powerful reduction is the best demonstrated major benefit of oral contraception. This protection is especially observed in nulliparous and seems to persist for many years after the discontinuation of medication.

The use of oral contraceptives in women over age 35 years

1995 ◽  
Vol 4 (2) ◽  
pp. 115-120
Author(s):  
Robert F Casper ◽  
Selim Senoz ◽  
Avraham Ben-Chetrit
Keyword(s):  
Cardiovascular Disease ◽  
Oral Contraceptive ◽  
Oral Contraceptives ◽  
Contraceptive Use ◽  
Older Woman ◽  
Oral Contraceptive Use ◽  
Increased Risk ◽  
Potential Risks ◽  
Europe Today ◽  
The Impact

Oral contraceptives remain the most widely used form of contraception in North America and Europe today. In spite of the concerns of many women relating to the potential risks of these preparations, recent data have demonstrated that currently available oral contraceptives are safe, with no increased risk of cardiovascular disease or cancer in nonsmoking women. The present review will focus on the impact of oral contraceptive use in the older woman, including a discussion of the noncontraceptive health benefits of oral contraceptives.

Postscript: starting oral contraceptives (25 May, page 41)

1992 ◽  
Vol 30 (14) ◽  
pp. 56.1-56
Keyword(s):  
Breast Cancer ◽  
Oral Contraceptives ◽  
Contraceptive Use ◽  
Causal Relation ◽  
Case Control ◽  
Term Pregnancy ◽  
Oral Contraceptive Use ◽  
Increased Risk ◽  
The Uk

In our article on oral contraceptives (OCs) we state that ‘oral contraceptives increase the risk of breast cancer with long-term use but reduce the risk of endometrial and ovarian cancer’. Some commentators have questioned the breast cancer risk. The UK National Case-Control (UKNCC) study, which looked at oral contraceptive use in women with breast cancer diagnosed before age 36, found a trend for increased risk associated with duration of use.1 ‘The simplest and most plausible explanation’, say the authors of the study, ‘must be that there is a substantial causal relation between prolonged use and breast cancer in young women.’ The increased risk seems to be associated particularly with OC use before the first full-term pregnancy.2 Several studies found no excess risk in OC users aged 45 or over, few of whom had taken the pill before their first pregnancy.3–5 In the UKNCC study the relative risk of breast cancer was 1.43 after 4–8 years’ use and 1.74 after more than 8 years’ use. In broad terms this means that three women in 1000 who use oral contraceptives for 4 or more years might be expected to be under treatment for breast cancer by age 36, compared with two per 1000 non-users.

The Effect of Grp78 Inhibition on Tissue Factor Gene Expression, Procoagulant Activity, and Factor Xa Generation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1924-1924
Author(s):  
Gourab Bhattacharjee ◽  
Jasimuddin Ahamed ◽  
Brian Pedersen ◽  
Amr El-Sheikh ◽  
Cheng Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Surface ◽  
Tissue Factor ◽  
Factor Xa ◽  
Cell Types ◽  
Procoagulant Activity ◽  
Coagulation Cascade ◽  
Clotting Factor ◽  
Tf Gene

Abstract In vivo biopanning with phage displayed peptide libraries has generated a group of peptide probes which bind selectively to the surface of atherosclerotic plaque endothelium. The highest affinity peptide, EKO130, binds to the 78 kDa glucose regulated protein (Grp78). Grp78 has been demonstrated to play a role in numerous pathological processes as well as a possible role in the local cell surface regulation of the coagulation cascade. The goal of this study is to determine the role of Grp78 in coagulation including plasma clotting, factor Xa (Xa) generation, and tissue factor (TF) gene expression. siRNA mediated inhibition of Grp78 results in a marked increase in TF gene expression in bEND.3 endothelial cells and RAW macrophage-like cells. Antibody mediated inhibition of cell surface Grp78 results in increased TF procoagulant activity and TF-dependent Xa generation in both the endothelial and macrophage cell types. These studies are consistent with results from another laboratory demonstrating that Grp78 over-expression inhibits TF mediated initiation and support of the coagulation protease cascade. Thus, our work indicates that Grp78 suppresses TF at both the functional and molecular level by inhibiting both its thrombogenic potential and gene expression.

scholarly journals Hematopoietic and nonhematopoietic cell tissue factor activates the coagulation cascade in endotoxemic mice

Blood ◽  
2010 ◽  
Vol 116 (5) ◽  
pp. 806-814 ◽  
Author(s):  
Rafal Pawlinski ◽  
Jian-Guo Wang ◽  
A. Phillip Owens ◽  
Julie Williams ◽  
Silvio Antoniak ◽  
...  
Keyword(s):  
Mouse Model ◽  
Tissue Factor ◽  
Myeloid Cells ◽  
Cell Types ◽  
Selective Inhibition ◽  
Coagulation Cascade ◽  
Cell Type ◽  
Relative Contribution ◽  
Cell Tissue ◽  
Tf Gene

Tissue factor (TF) is the primary activator of the coagulation cascade. During endotoxemia, TF expression leads to disseminated intravascular coagulation. However, the relative contribution of TF expression by different cell types to the activation of coagulation has not been defined. In this study, we investigated the effect of either a selective inhibition of TF expression or cell type-specific deletion of the TF gene (F3) on activation of coagulation in a mouse model of endotoxemia. We found that inhibition of TF on either hematopoietic or nonhematopoietic cells reduced plasma thrombin-antithrombin (TAT) levels 8 hours after administration of bacterial lipopolysaccharide (LPS). In addition, plasma TAT levels were significantly reduced in endotoxemic mice lacking the TF gene in either myeloid cells (TFflox/flox,LysMCre mice) or in both endothelial cells (ECs) and hematopoietic cells (TFflox/flox,Tie-2Cre mice). However, deletion of the TF gene in ECs alone had no effect on LPS-induced plasma TAT levels. Similar results were observed in mice lacking TF in vascular smooth muscle cells. Finally, we found that mouse platelets do not express TF pre-mRNA or mRNA. Our data demonstrate that in a mouse model of endotoxemia activation of the coagulation cascade is initiated by TF expressed by myeloid cells and an unidentified nonhematopoietic cell type(s).

Gall-Stones and Oral Contraceptives

1975 ◽  
Vol 3 (2) ◽  
pp. 59-62 ◽  
Author(s):  
J M T Howat ◽  
C B Jones ◽  
P F Schofield
Keyword(s):  
Oral Contraceptives ◽  
Young Women ◽  
Contraceptive Use ◽  
Stone Formation ◽  
Gall Stone ◽  
Hormonal Changes ◽  
Oral Contraceptive Use ◽  
Gall Stones ◽  
Menopausal Women ◽  
Physical And Chemical

An investigation into oral contraceptive use in female patients with gallstones has been undertaken. Comparison between a group of 50 young women aged 20-45 years with gall-stones and a group of young women of similar age and parity without gall-stones, shows a significantly higher incidence of contraceptive use in the gall-stone patients (p > 0·001). It is suggested that oral contraceptives may predispose pre-menopausal women to gall-stone formation and this is discussed in relationship to the physical and chemical alterations in biliary secretion produced by hormonal changes.

Oral contraceptive use and risk of suicidal behavior among young women

2020 ◽  
pp. 1-8
Author(s):  
Alexis C. Edwards ◽  
Sara Larsson Lönn ◽  
Casey Crump ◽  
Eve K. Mościcki ◽  
Jan Sundquist ◽  
...  
Keyword(s):  
Oral Contraceptive ◽  
Oral Contraceptives ◽  
Young Women ◽  
Suicidal Behavior ◽  
Contraceptive Use ◽  
Cox Proportional Hazards ◽  
Causal Mechanism ◽  
Parental History ◽  
Oral Contraceptive Use ◽  
Increased Risk

Abstract Background Oral contraceptive use has been previously associated with an increased risk of suicidal behavior in some, but not all, samples. The use of large, representative, longitudinally-assessed samples may clarify the nature of this potential association. Methods We used Swedish national registries to identify women born between 1991 and 1995 (N = 216 702) and determine whether they retrieved prescriptions for oral contraceptives. We used Cox proportional hazards models to test the association between contraceptive use and first observed suicidal event (suicide attempt or death) from age 15 until the end of follow-up in 2014 (maximum age 22.4). We adjusted for covariates, including mental illness and parental history of suicide. Results In a crude model, use of combination or progestin-only oral contraceptives was positively associated with suicidal behavior, with hazard ratios (HRs) of 1.73–2.78 after 1 month of use, and 1.25–1.82 after 1 year of use. Accounting for sociodemographic, parental, and psychiatric variables attenuated these associations, and risks declined with increasing duration of use: adjusted HRs ranged from 1.56 to 2.13 1 month beyond the initiation of use, and from 1.19 to 1.48 1 year after initiation of use. HRs were higher among women who ceased use during the observation period. Conclusions Young women using oral contraceptives may be at increased risk of suicidal behavior, but risk declines with increased duration of use. Analysis of former users suggests that women susceptible to depression/anxiety are more likely to cease hormonal contraceptive use. Additional studies are necessary to determine whether the observed association is attributable to a causal mechanism.

scholarly journals Coagulation abnormalities in SARS-CoV-2 infection: overexpression tissue factor

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Zahra Eslamifar ◽  
Mahin Behzadifard ◽  
Masoud Soleimani ◽  
Saba Behzadifard
Keyword(s):  
Tissue Factor ◽  
Proinflammatory Cytokines ◽  
Viral Infections ◽  
Multiorgan Failure ◽  
Critical Role ◽  
Coagulation Cascade ◽  
Coagulation System ◽  
Alveolar Cells ◽  
Increased Risk ◽  
Life Threatening

AbstractAmong the pathways and mediators that may be dysregulated in COVID-19 infection, there are proinflammatory cytokines, lymphocyte apoptosis, and the coagulation cascade. Venous and arterial thromboembolisms also are frequent in COVID-19 patients with the increased risk of some life-threatening complications such as pulmonary embolism, myocardial infarction, and ischemic stroke. In this regard, overproduction of proinflammatory cytokines such as IL-6, IL-1β, and TNF-α induce cytokine storms, increase the risk of clot formation, platelet activation, and multiorgan failure that may eventually lead to death among these patients. Surface S protein of SARS-CoV-2 binds to its target transmembrane receptor, named as angiotensin converting enzyme 2 (ACE2(, on various cells such as lymphocyte, alveolar cells, monocytes/macrophages, and platelets. Notably, the activation of the coagulation cascade occurs through tissue factor (TF)/FVIIa-initiated hemostasis. Accordingly, TF plays the major role in the activation of coagulation system during viral infection. In viral infections, the related coagulopathy multiple factors such as inflammatory cytokines and viral specific TLRs are involved, which consequently induce TF expression aberrantly. SARS-COV-2 may directly infect monocytes/ macrophages. In addition, TF expression/release from these cells may play a critical role in the development of COVID-19 coagulopathy. In this regard, the use of TF- VIIa complex inhibitor may reduce the cytokine storm and mortality among COVID-19 patients.

Effect of Heparanase and Heparan Sulfate Chains in Hemostasis

2021 ◽  
Vol 47 (03) ◽  
pp. 254-260
Author(s):  
Yona Nadir
Keyword(s):  
Cell Surface ◽  
Heparan Sulfate ◽  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Contraceptive Use ◽  
Coagulation System ◽  
Endothelial Cell Surface ◽  
Oral Contraceptive Use ◽  
Increased Risk ◽  
Tissue Factor Pathway

AbstractHeparanase, the only mammalian enzyme known to degrade heparan sulfate chains, affects the hemostatic system through several mechanisms. Along with the degrading effect, heparanase engenders release of syndecan-1 from the cell surface and directly enhances the activity of the blood coagulation initiator, tissue factor, in the coagulation system. Upregulation of tissue factor and release of tissue factor pathway inhibitor from the cell surface contribute to the prothrombotic effect. Tissue factor pathway inhibitor and the strongest physiological anticoagulant antithrombin are attached to the endothelial cell surface by heparan sulfate. Hence, degradation of heparan sulfate induces further release of these two natural anticoagulants from endothelial cells. Elevated heparanase procoagulant activity and heparan sulfate chain levels in plasma, demonstrated in cancer, pregnancy, oral contraceptive use, and aging, could suggest a potential mechanism for increased risk of thrombosis in these clinical settings. In contrast to the blood circulation, accumulation of heparan sulfate chains in transudate and exudate pleural effusions induces a local anticoagulant milieu. The anticoagulant effect of heparan sulfate chains in other closed spaces such as peritoneal or subdural cavities should be further investigated.

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