Tissue Factor: A Critical Role in Inflammation and Cancer

A series of coordinated enzymatic reactions takes place in the body whenever blood clots. The major physiological initiator of these reactions is a membrane-bound glycoprotein known as tissue factor (TF), which is normally separated from the bloodstream by the vascular endothelium. Bleeding, caused by injury or tissue damage, activates a complex enzyme cascade as TF becomes exposed to the bloodstream. In disease states, leukocytes or the vascular endothelium may abnormally express TF to cause intravascular coagulation. The blood-coagulation cascade is also relevant to diseases such as hemophilia, in which patients are deficient in blood proteins necessary for clotting, and is linked to vascular diseases such as heart attack and stroke, in which clotting can lead to the occlusion of blood vessels. Coagulation is also activated in inflammation and cancer. In this article, we discuss characteristics of TF and review its role in inflammation and cancer.

Download Full-text

REPEATED LONG-TERM SPACE FLIGHTS: PROTEOMIC INVESTIGATIONS OF COSMONAUTS' BLOOD

Aerospace and Environmental Medicine ◽

10.21687/0233-528x-2020-54-5-15-22 ◽

2020 ◽

Vol 54 (5) ◽

pp. 15-22

Author(s):

I.M. Larina ◽

◽

D.N. Kashirina ◽

K.S. Kireev ◽

A.I. Grigoriev ◽

...

Keyword(s):

Bone Structure ◽

Space Station ◽

The Body ◽

Coagulation Cascade ◽

Chemical Components ◽

Blood Proteins ◽

Blood Indices ◽

Before And After ◽

Biochemical Indices

We performed the first ever comparative analysis of modifications in the proteome, ionogram and some other blood plasma biochemical indices of 18 male cosmonauts (44 ± 6 years of age) before and after maiden or repeated long-term missions to the Russian segment of the International space station (ISS RS). Levels of proteins, substrates and ions as well as chemical components were measured using the LC-MS-based proteomics and routine biochemical techniques. A total of 256 to 281 indices were investigated with the methods of descriptive statistic, regression analysis, and access to bioinformatics resources. It was shown that blood indices recovery from the maiden and repeated missions reflects changes in the body systems and goes at a various speed. The results of measurements made prior to launch and on day 7 after landing are dependent on the number of missions. The bioinformatics techniques showed that after maiden missions both the mediator proteins of alkaline phosphatase (AP) and blood proteins with reliably changing concentrations are associated with the bio-processes including stress, metabolism and DNA reparation, apoptosis, catabolism and proteolysis. During early re-adaptation from repeated missions the AP level was affected by bone remodeling, phosphorylation, angiogenesis and coagulation cascade suggesting a distinct and urgent trigger of the processes of bone structure and mineralization.

Download Full-text

Role of Cell Surface Lipids and Thiol-Disulphide Exchange Pathways in Regulating the Encryption and Decryption of Tissue Factor

Thrombosis and Haemostasis ◽

10.1055/s-0039-1681102 ◽

2019 ◽

Vol 119 (06) ◽

pp. 860-870 ◽

Cited By ~ 6

Author(s):

Shabbir A. Ansari ◽

Usha R. Pendurthi ◽

L. Vijaya Mohan Rao

Keyword(s):

Cell Surface ◽

Tissue Factor ◽

Cell Injury ◽

Critical Role ◽

The Body ◽

Resting Cells ◽

Aberrant Expression ◽

Outer Leaflet ◽

Coagulant Activity ◽

Encryption And Decryption

AbstractTissue factor (TF), a transmembrane glycoprotein, is the cellular receptor of the coagulation factors VII (FVII) and VIIa (FVIIa). The formation of TF–FVIIa complex triggers the initiation of the blood coagulation pathway. TF plays an essential role in haemostasis, but an aberrant expression of TF activity contributes to thrombotic disorders. In health, TF pro-coagulant activity on cells is controlled tightly to allow sufficient coagulant activity to achieve haemostasis but not to cause thrombosis. It is achieved largely by selective localization of TF in the body and encryption of TF at the cell surface. A vast majority of TF on resting cells exists in an encrypted state with minimal pro-coagulant activity but becomes pro-thrombotic following cell injury or activation. At present, the mechanisms that are responsible for TF encryption and activation (decryption) are not entirely clear, but recent studies provide important mechanistic insights into these processes. To date, externalization of phosphatidylserine to the outer leaflet and thiol-disulphide exchange pathways that either turn on and off the allosteric disulphide bond in TF are shown to play a major role in regulating TF pro-coagulant activity on cell surfaces. Recent studies showed that sphingomyelin, a major phospholipid in the outer leaflet of plasma membrane, plays a critical role in the encryption of TF in resting cells. The present review provides an overview of recent literature on the above-described mechanisms of TF encryption and decryption with a particular emphasis on our recent findings.

Download Full-text

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

Thrombosis Journal ◽

10.1186/s12959-020-00250-x ◽

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.

Download Full-text

A Simplified and High-Throughput Chromogenic Assay for Testing Tissue Factor–Dependent Procoagulant Activity

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057110396370 ◽

2011 ◽

Vol 16 (3) ◽

pp. 295-302 ◽

Cited By ~ 8

Author(s):

Wenwen Jiang ◽

Junping Kou ◽

Shengtao Yuan ◽

Li Sun ◽

Boyang Yu

Keyword(s):

Cardiovascular Diseases ◽

Tissue Factor ◽

High Throughput ◽

Critical Role ◽

Screening Method ◽

Coagulation Factors ◽

Coagulation Cascade ◽

Chromogenic Substrate ◽

Human Monocytes ◽

Chromogenic Assay

Tissue factor (TF), the primary initiator of the coagulation cascade, plays a critical role in hemostasis and thrombosis, and inhibition of TF activity appears to be an attractive target for the treatment of cardiovascular diseases. However, few selective small-molecule inhibitors of TF are available, and the present assays for measuring TF activity are relatively expensive and complex. The authors present a simple and high-throughput chromogenic assay for screening TF inhibitors based on using commercial human prothrombin complex instead of purified coagulation factors, reducing the dosage, and performing with a one-stage procedure. In the optimized assay, <45 µL cell lysates was incubated with Tris-CaCl2 buffer (pH 7.3) containing human prothrombin complex at 37°C for 15 min in 96-well or 384-well plates. Tris-EDTA buffer (pH 8.4) containing chromogenic substrate Xa was then added and the absorbance measured at 405 nm. This simplified assay was more sensitive or precise than some reported methods for TF procoagulant activities. Two known active compounds (curcumin and simvastatin) inhibiting TF activity were tested by the simplified assay to validate the screening method. Furthermore, berberine and cryptotanshinone suppressed TF activity induced by lipopolysaccharides in human monocytes by this assay and might be promising new TF inhibitors.

Download Full-text

Extracellular phosphate sensing in mammals: what do we know?

Journal of Molecular Endocrinology ◽

10.1530/jme-20-0121 ◽

2020 ◽

Vol 65 (3) ◽

pp. R53-R63 ◽

Cited By ~ 1

Author(s):

Laurent Beck ◽

Sarah Beck-Cormier

Keyword(s):

Fibroblast Growth Factor 23 ◽

Critical Role ◽

The Body ◽

Disease States ◽

Calcium Sensing ◽

Phosphate Sensing ◽

Life Threatening ◽

Body Level ◽

Stage Renal Disease ◽

End Stage

The critical role of phosphate (Pi) in countless biological processes requires the ability to control its concentration both intracellularly and extracellularly. At the body level, this concentration is finely regulated by numerous hormones, primarily parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). While this control of the body’s Pi homeostasis is now well documented, knowledge of the mechanisms that allow the cell and the body to detect extracellular Pi variations is much less known. These systems are well described in bacteria, yeasts and plants, but as will be discussed in this review, knowledge obtained from these organisms is not entirely relevant to the requirements of Pi biology in mammals. In this review, we present the latest findings on extracellular Pi sensing in mammals, and describe the mammalian Pi sensors identified to date, such as SLC20A1 (PIT1)/SLC20A2 (PIT2) heterodimers and the calcium-sensing receptor (CaSR). While there are many questions remaining to be resolved, a clarification of the Pi sensing mechanisms in mammals is critical to understanding the deregulation of Pi balance in certain life-threatening disease states, such as end-stage renal disease and associated vascular calcifications, and to proposing relevant therapeutic approaches.

Download Full-text

Updating long-held assumptions about fat stigma: For women, body shape plays a critical role

10.31234/osf.io/b6t7a ◽

2020 ◽

Author(s):

Jaimie Krems ◽

Steven L. Neuberg

Keyword(s):

Body Shape ◽

Critical Role ◽

The Body ◽

Theoretical Assumption ◽

Obesity Stigma ◽

Obese Female ◽

Three Samples ◽

Female Bodies ◽

Different Parts ◽

Fat Stigma

Heavier bodies—particularly female bodies—are stigmatized. Such fat stigma is pervasive, painful to experience, and may even facilitate weight gain, thereby perpetuating the obesity-stigma cycle. Leveraging research on functionally distinct forms of fat (deposited on different parts of the body), we propose that body shape plays an important but largely underappreciated role in fat stigma, above and beyond fat amount. Across three samples varying in participant ethnicity (White and Black Americans) and nation (U.S., India), patterns of fat stigma reveal that, as hypothesized, participants differently stigmatized equally-overweight or -obese female targets as a function of target shape, sometimes even more strongly stigmatizing targets with less rather than more body mass. Such findings suggest value in updating our understanding of fat stigma to include body shape and in querying a predominating, but often implicit, theoretical assumption that people simply view all fat as bad (and more fat as worse).

Download Full-text

Antipyretic Plants: An Updated Review

Current Bioactive Compounds ◽

10.2174/1573407215666190401151844 ◽

2020 ◽

Vol 16 (1) ◽

pp. 4-12

Author(s):

Vandana Garg ◽

Rohit Dutt

Keyword(s):

Side Effects ◽

Body Temperature ◽

Medicinal Plants ◽

Inflammatory Mediators ◽

Review Paper ◽

The Body ◽

Hypothalamic Area ◽

Antipyretic Activity ◽

Disease States ◽

Elevated Body Temperature

Background: Fever, is known as pyrexia, may occur due to infection, inflammation, or any tissue damage and disease states. Normally, the infected or damaged tissue initiates the enhanced formation of pro-inflammatory mediators like cytokines which further increases the synthesis of prostaglandin E2 (PgE2) near the hypothalamic area and thereby trigger the hypothalamus to elevate the body temperature. Objective: Antipyretics are the agents which reduce the elevated body temperature. The most commonly used antipyretic agent, paracetamol, may be fatal due to its side effects. Methods: In this review paper, Chemical Abstracts, Google Scholar, PubMed, and Science Direct were the sources for the published article to collect information regarding antipyretic activity. Results: This review compiles the antipyretic plants that may be useful to treat fever due to various diseases. Conclusion: These medicinal plants could be good alternatives for traditional allopathic antipyretics.

Download Full-text

PPARs as Metabolic Sensors and Therapeutic Targets in Liver Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms22158298 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8298

Author(s):

Hugo Christian Monroy-Ramirez ◽

Marina Galicia-Moreno ◽

Ana Sandoval-Rodriguez ◽

Alejandra Meza-Rios ◽

Arturo Santos ◽

...

Keyword(s):

Liver Diseases ◽

Metabolic Regulation ◽

Structural Changes ◽

Critical Role ◽

The Body ◽

Molecular Characteristics ◽

Signal Pathways ◽

Virus Infections ◽

Physiological Processes ◽

Hepatic Level

Carbohydrates and lipids are two components of the diet that provide the necessary energy to carry out various physiological processes to help maintain homeostasis in the body. However, when the metabolism of both biomolecules is altered, development of various liver diseases takes place; such as metabolic-associated fatty liver diseases (MAFLD), hepatitis B and C virus infections, alcoholic liver disease (ALD), and in more severe cases, hepatocelular carcinoma (HCC). On the other hand, PPARs are a family of ligand-dependent transcription factors with an important role in the regulation of metabolic processes to hepatic level as well as in other organs. After interaction with specific ligands, PPARs are translocated to the nucleus, undergoing structural changes to regulate gene transcription involved in lipid metabolism, adipogenesis, inflammation and metabolic homeostasis. This review aims to provide updated data about PPARs’ critical role in liver metabolic regulation, and their involvement triggering the genesis of several liver diseases. Information is provided about their molecular characteristics, cell signal pathways, and the main pharmacological therapies that modulate their function, currently engaged in the clinic scenario, or in pharmacological development.

Download Full-text

Reduced Flow-Mediated Dilatation Is Not Related to COVID-19 Severity Three Months after Hospitalization for SARS-CoV-2 Infection

Journal of Clinical Medicine ◽

10.3390/jcm10061318 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1318

Author(s):

Marianne Riou ◽

Walid Oulehri ◽

Cedric Momas ◽

Olivier Rouyer ◽

Fabienne Lebourg ◽

...

Keyword(s):

Vascular Endothelium ◽

Matched Control ◽

Acute Infection ◽

Critical Role ◽

Lung Damage ◽

Vascular Effect ◽

Flow Mediated Dilatation ◽

Artery Flow

The coronavirus disease 2019 (COVID-19) pandemic has spread rapidly worldwide, with more than two million deaths. Evidence indicates the critical role of the vascular endothelium in its pathophysiology but, like potential changes in functional vasodilation, the vascular effect of SARS-CoV-2 at a given distance from the acute infection is largely unknown. We assessed brachial artery flow-mediated dilatation (FMD) in 27 COVID-19 patients needing conventional or intensive care unit hospitalization, three months after SARS-CoV-2 infection diagnosis and in nine age- and sex- matched control subjects. Interestingly, the FMD was lower in COVID-19 patients as compared to controls (8.2 (7.2–8.9) vs. 10.3 (9.1–11.7)); p = 0.002, and half of the hospitalized COVID-19 survivors presented with a reduced FMD < 8% at three months of COVID-19 onset. Impaired FMD was not associated with severe or critical SARS-CoV-2 infection, reflected by ICU hospitalization, total hospitalization duration, or severity of lung damage. In conclusion, reduced FMD is often observed even three months after hospitalization for SARS-CoV-2 infection, but such alteration predominantly appears to not be related to COVID-19 severity. Longer and larger follow-up studies will help to clarify the potential prognosis value of FMD among COVID-19 patients, as well as to further determine the mechanisms involved.

Download Full-text