A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation.
A family of proteinase-activated receptors that are specific for THROMBIN. They are found primarily on PLATELETS and on ENDOTHELIAL CELLS. Activation of thrombin receptors occurs through the proteolytic action of THROMBIN, which cleaves the N-terminal peptide from the receptor to reveal a new N-terminal peptide that is a cryptic ligand for the receptor. The receptors signal through HETEROTRIMERIC GTP-BINDING PROTEINS. Small synthetic peptides that contain the unmasked N-terminal peptide sequence can also activate the receptor in the absence of proteolytic activity.
A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation.
An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.
A metallocarboxypeptidase that removes C-terminal lysine and arginine from biologically active peptides and proteins thereby regulating their activity. It is a zinc enzyme with no preference shown for lysine over arginine. Pro-carboxypeptidase U in human plasma is activated by thrombin or plasmin during clotting to form the unstable carboxypeptidase U.
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
The process of the interaction of BLOOD COAGULATION FACTORS that results in an insoluble FIBRIN clot.
Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.
Constituent composed of protein and phospholipid that is widely distributed in many tissues. It serves as a cofactor with factor VIIa to activate factor X in the extrinsic pathway of blood coagulation.
Endogenous substances, usually proteins, that are involved in the blood coagulation process.
A plasma alpha 2 glycoprotein that accounts for the major antithrombin activity of normal plasma and also inhibits several other enzymes. It is a member of the serpin superfamily.
Single-chain polypeptides of about 65 amino acids (7 kDa) from LEECHES that have a neutral hydrophobic N terminus, an acidic hydrophilic C terminus, and a compact, hydrophobic core region. Recombinant hirudins lack tyr-63 sulfation and are referred to as 'desulfato-hirudins'. They form a stable non-covalent complex with ALPHA-THROMBIN, thereby abolishing its ability to cleave FIBRINOGEN.
The process which spontaneously arrests the flow of BLOOD from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements (eg. ERYTHROCYTE AGGREGATION), and the process of BLOOD COAGULATION.
A disorder characterized by procoagulant substances entering the general circulation causing a systemic thrombotic process. The activation of the clotting mechanism may arise from any of a number of disorders. A majority of the patients manifest skin lesions, sometimes leading to PURPURA FULMINANS.
Two small peptide chains removed from the N-terminal segment of the beta chains of fibrinogen by the action of thrombin. Each peptide chain contains 20 amino acid residues. The removal of fibrinopeptides B is not required for coagulation.
A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia.
Venous vessels in the umbilical cord. They carry oxygenated, nutrient-rich blood from the mother to the FETUS via the PLACENTA. In humans, there is normally one umbilical vein.
Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.
Formation and development of a thrombus or blood clot in the blood vessel.
A high-molecular-weight plasma protein, produced by endothelial cells and megakaryocytes, that is part of the factor VIII/von Willebrand factor complex. The von Willebrand factor has receptors for collagen, platelets, and ristocetin activity as well as the immunologically distinct antigenic determinants. It functions in adhesion of platelets to collagen and hemostatic plug formation. The prolonged bleeding time in VON WILLEBRAND DISEASES is due to the deficiency of this factor.
Proteins prepared by recombinant DNA technology.
Two small peptide chains removed from the N-terminal segment of the alpha chains of fibrinogen by the action of thrombin during the blood coagulation process. Each peptide chain contains 18 amino acid residues. In vivo, fibrinopeptide A is used as a marker to determine the rate of conversion of fibrinogen to fibrin by thrombin.
Heat- and storage-labile plasma glycoprotein which accelerates the conversion of prothrombin to thrombin in blood coagulation. Factor V accomplishes this by forming a complex with factor Xa, phospholipid, and calcium (prothrombinase complex). Deficiency of factor V leads to Owren's disease.
The natural enzymatic dissolution of FIBRIN.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Activated form of factor V. It is an essential cofactor for the activation of prothrombin catalyzed by factor Xa.
Enzymes which catalyze the elimination of delta-4,5-D-glucuronate residues from polysaccharides containing 1,4-beta-hexosaminyl and 1,3-beta-D-glucuronosyl or 1,3-alpha-L-iduronosyl linkages thereby bringing about depolymerization. EC 4.2.2.4 acts on chondroitin sulfate A and C as well as on dermatan sulfate and slowly on hyaluronate. EC 4.2.2.5 acts on chondroitin sulfate A and C.
A layer of epithelium that lines the heart, blood vessels (ENDOTHELIUM, VASCULAR), lymph vessels (ENDOTHELIUM, LYMPHATIC), and the serous cavities of the body.
The rate dynamics in chemical or physical systems.
A vascular anomaly due to proliferation of BLOOD VESSELS that forms a tumor-like mass. The common types involve CAPILLARIES and VEINS. It can occur anywhere in the body but is most frequently noticed in the SKIN and SUBCUTANEOUS TISSUE. (from Stedman, 27th ed, 2000)
A ZINC-dependent carboxypeptidase primary found in the DIGESTIVE SYSTEM. The enzyme catalyzes the preferential cleavage of a C-terminal peptidyl-L-lysine or arginine. It was formerly classified as EC 3.4.2.2 and EC 3.4.12.3.
Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)

Novel proteoglycan linkage tetrasaccharides of human urinary soluble thrombomodulin, SO4-3GlcAbeta1-3Galbeta1-3(+/-Siaalpha2-6)Galbeta1-4Xyl. (1/506)

O-linked sugar chains with xylose as a reducing end linked to human urinary soluble thrombomodulin were studied. Sugar chains were liberated by hydrazinolysis followed by N-acetylation and tagged with 2-aminopyridine. Two fractions containing pyridylaminated Xyl as a reducing end were collected. Their structures were determined by partial acid hydrolysis, two-dimensional sugar mapping combined with exoglycosidase digestions, methylation analysis, mass spectrometry, and NMR as SO4-3GlcAbeta1-3Galbeta1-3(+/-Siaalpha2-6)Galbeta1+ ++-4Xyl. These sugar chains could bind to an HNK-1 monoclonal antibody. This is believed to be the first example of a proteoglycan linkage tetrasaccharide with glucuronic acid 3-sulfate and sialic acid.  (+info)

Reconstitution of the human endothelial cell protein C receptor with thrombomodulin in phosphatidylcholine vesicles enhances protein C activation. (2/506)

Blocking protein C binding to the endothelial cell protein C receptor (EPCR) on the endothelium is known to reduce protein C activation rates. Now we isolate human EPCR and thrombomodulin (TM) and reconstitute them into phosphatidylcholine vesicles. The EPCR increases protein C activation rates in a concentration-dependent fashion that does not saturate at 14 EPCR molecules/TM. Without EPCR, the protein C concentration dependence fits a single class of sites (Km = 2.17 +/- 0.13 microM). With EPCR, two classes of sites are apparent (Km = 20 +/- 15 nM and Km = 3.2 +/- 1.7 microM). Increasing the EPCR concentration at a constant TM concentration increases the percentage of high affinity sites. Holding the TM:EPCR ratio constant while decreasing the density of these proteins results in a decrease in the EPCR enhancement of protein C activation, suggesting that there is little affinity of the EPCR for TM. Negatively charged phospholipids also enhance protein C activation. EPCR acceleration of protein C activation is blocked by anti-EPCR antibodies, but not by annexin V, whereas the reverse is true with negatively charged phospholipids. Human umbilical cord endothelium expresses approximately 7 times more EPCR than TM. Anti-EPCR antibody reduces protein C activation rates 7-fold over these cells, whereas annexin V is ineffective, indicating that EPCR rather than negatively charged phospholipid provide the surface for protein C activation. EPCR expression varies dramatically among vascular beds. The present results indicate that the EPCR concentration will determine the effectiveness of the protein C activation complex.  (+info)

Arterial flow conditions downregulate thrombomodulin on saphenous vein endothelium. (3/506)

BACKGROUND: The antithrombogenic properties of venous endothelium may be attenuated when vein is implanted in the arterial circulation. Such changes may facilitate thrombosis, which is the final common pathway for saphenous vein arterial bypass graft occlusion. METHODS AND RESULTS: Using human saphenous vein in a validated ex vivo flow circuit, we investigated (1) the possibility that arterial flow conditions (mean pressure, 100 mm Hg, 90 cpm, approximately 200 mL/min) alter the concentration of proteins involved in regulating thrombosis at the vessel wall and (2) the influence of ion channel blockade on such effects. Concentrations of thrombomodulin and tissue factor were quantified by Western blotting (ratio of von Willebrand factor staining) and immunohistochemistry (as a percentage of CD31-staining area). Thrombomodulin concentrations after 90 minutes of venous and arterial flow conditions were quantified by immunostaining (68.9+/-4.8% and 41.0+/-3.0% CD31, respectively; P<0.01) and by Western blotting (1.35+/-0.20 and 0. 15+/-0.03 ratio of von Willebrand factor, respectively; P<0.01). The ability of endothelial cells to generate activated protein C also decreased from 62+/-14 to 19+/-10 ng. min-1. 1000 cells-1 (P=0.01). The significant reduction in thrombomodulin was attenuated if calcium was removed from the perfusate but not by external vein stenting. Inclusion in the vein perfusate of drugs that reduce calcium entry (including Gd3+, to block stretch-activated ion channels, and nifedipine) abolished the reduction in thrombomodulin concentration observed after arterial flow conditions. In freshly excised vein, negligible concentrations of tissue factor were detected on the endothelium and concentrations did not increase after 90 minutes of arterial flow conditions, although the inclusion of nifedipine caused the immunostaining to increase from 3.0+/-0.4% to 8.5+/-0.7% CD31 (P<0.02). CONCLUSIONS: In saphenous vein endothelium exposed to arterial flow conditions, there is rapid downregulation of thrombomodulin, sufficient to limit protein C activation, by a calcium-dependent mechanism.  (+info)

Serum levels of thrombomodulin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin in the acute phase of Plasmodium vivax malaria. (4/506)

Elevated plasma or serum levels of thrombomodulin (TM), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin have been reported in several diseases. However, plasma or serum levels of TM, ICAM-1, VCAM-1, and E-selectin have not been investigated in the acute phase of Plasmodium vivax malaria. Serum TM, ICAM-1, VCAM-1, E-selectin, and creatinine levels were determined in six Japanese patients in the acute phase of vivax malaria and in seven healthy Japanese controls. Parasitemias of the peripheral blood were < 0.1% in five patients and 0.8% in one patient. The patients' mean +/- SD serum levels of TM, ICAM-1, VCAM-1, and E-selectin were 5.7 +/- 1.3 Fujirebio units/ml, 709 +/- 397 ng/ml, 2,112 +/- 782 ng/ml, and 99 +/- 28 ng/ml, respectively, and all were significantly greater than those in the controls (TM; P < 0.005, ICAM-1; P < 0.025, VCAM-1; P < 0.005, E-selectin; P < 0.025). However, no significant difference was identified between patients and controls for serum creatinine values. The serum levels of TM and VCAM-1 were not related to parasitemia. The elevation of serum TM levels suggests that endothelial cell damage occurs in the acute phase of vivax malaria.  (+info)

Allosteric modulation of BPTI interaction with human alpha- and zeta-thrombin. (5/506)

In this study, thrombin interaction with the basic pancreatic trypsin inhibitor (BPTI) was investigated in the presence of different allosteric modulators of thrombin, that is the C-terminal hirudin peptide 54-65 (Hir54-65), a recombinant thrombomodulin form (TMEGF4-6) and Na+. BPTI binding to alpha-thrombin is positively linked to Na+. Under low sodium concentration (5 mM Na+) the BPTI affinity for alpha-thrombin was roughly threefold lower than in the presence of 150 mM sodium (Ki = 320 microM vs. 100 microM). The hirudin fragment, which binds to the fibrinogen recognition site (FRS) of thrombin, induced a progressive and saturable decrease (3.6-fold) of alpha-thrombin affinity for BPTI, whereas the thrombomodulin peptide, which binds to a more extended region of FRS, caused a 5.5-fold increase of the enzyme affinity for the inhibitor. The opposite effect exerted by Hir54-65 and TMEGF4-6 was also observed for BPTI interaction with zeta-thrombin, in which the amidic bond between W148 and T149 is cleaved. However, in this case the effect by Hir54-65 and TMEGF4-6, although qualitatively similar to that observed with alpha-thrombin, had a smaller magnitude. Thrombin hydrolysis of Protein C was also differently affected by Hir54-65 and TMEGF4-6 peptides. While the latter enhanced the Protein C activation, the former caused a reduction of both alpha- and zeta-thrombin kcat/K(m)' for Protein C cleavage. These results showed that (a) Na+ facilitates BPTI interaction with thrombin; (b) Hir54-65 and TMEGF4-6, though sharing in part the same binding site at the thrombin FRS, can affect in opposite way thrombin's interaction with BPTI and Protein C; (c) such findings along with the results obtained with zeta-thrombin might be explained by admitting that the thermodynamic linkage between FRS and the critical W60-loop is also controlled by ligation and/or conformational state of the W148 insertion loop.  (+info)

Inflammation, sepsis, and coagulation. (6/506)

The molecular links between inflammation and coagulation are unquestioned. Inflammation promotes coagulation by leading to intravascular tissue factor expression, eliciting the expression of leukocyte adhesion molecules on the intravascular cell surfaces, and down regulating the fibrinolytic and protein C anticoagulant pathways. Thrombin, in turn, can promote inflammatory responses. This creates a cycle that logically progresses to vascular injury as occurs in septic shock. Most complex systems are regulated by product inhibition. This inflammation-coagulation cycle seems to follow this same principle with the protein C pathway serving as the regulatory mechanism. The molecular basis by which the protein C pathway functions as an anticoagulant is relatively well established compared to the mechanisms involved in regulating inflammation. As one approach to identifying the mechanisms involved in regulating inflammation, we set out to identify novel receptors that could modulate the specificity of APC in a manner analogous to the mechanisms by which thrombomodulin modulates thrombin specificity. This approach led to the identification of an endothelial cell protein C receptor (EPCR). To understand the mechanism, we obtained a crystal structure of APC (lacking the Gla domain). The crystal structure reveals a deep groove in a location analogous to anion binding exosite 1 of thrombin, the location of interaction for thrombomodulin, platelet thrombin receptor and fibrinogen. Thrombomodulin blocks the activation of platelets and fibrinogen without blocking reactivity with chromogenic substrates or inhibitors. Similarly, in solution, EPCR blocks factor Va inactivation without modulating reactivity with protease inhibitors. Thus, these endothelial cell receptors for the protein C system share many properties in common including the ability to be modulated by inflammatory cytokines. Current studies seek to identify the substrate for the APC-EPCR complex as the next step in elucidating the mechanisms by which the protein C pathway modulates the response to injury and inflammation.  (+info)

Mutations in promoter region of thrombomodulin and venous thromboembolic disease. (7/506)

The present study was designed to analyze the thrombomodulin proximal promoter region spanning nucleotides -293 to -12 to search for polymorphisms that could modify thrombomodulin gene expression in patients with venous thromboembolic disease. The study population comprised 205 patients and 394 healthy subjects of similar age and sex distribution. No polymorphisms and only 1 point mutation (G-33A) were found. The G-33A mutation was present at the heterozygous state in 2 patients and in 1 control. Being more frequent in the patients (0.97%) than in the controls (0.25%), the G-33A mutation might be a risk factor for venous thrombosis. To investigate the effect of this mutation on the thrombomodulin promoter activity, the proximal promoter region of the gene (bearing or not bearing the G-33A mutation) was inserted into a promotorless expression vector, upstream of the firefly luciferase gene, and transiently transfected into EA.hy926 endothelial cells. Under the conditions of the assay, the G-33A mutation mildly decreased the promoter activity. This study confirms that abnormalities of the thrombomodulin proximal promoter are not frequent in patients with venous thromboembolism.  (+info)

cDNA cloning and sequencing, gene expression, and immunolocalization of thrombomodulin in the Sprague-Dawley rat. (8/506)

Thrombomodulin (TM), in addition to its significance in the protein C anticoagulant pathway and cardiovascular diseases, has recently been shown to play important roles in normal embryonic development, several inflammatory conditions, as well as in tumor biology and in the pathogenesis of chronic radiation toxicity. We cloned and sequenced the cDNA encoding the complete TM protein from the Sprague-Dawley rat. The cDNA sequence consisted of a 78-bp 5' non-coding region and a 1731-bp open reading frame encoding 577 amino acids. Comparison of the deduced amino acid sequences showed Sprague-Dawley rat TM to be 87% homologous with mouse and 70.3% with human TM. In addition to the previously described highly conserved region in the lectin-like domain, another region was found which possessed significant homology among the species and may be involved in regulating cell surface expression of TM. Primers and fluorogenic probe for 5' exonuclease-based real time RT-PCR detection (TaqMan PCR) were constructed based on the cDNA sequence information and used to determine steady-state TM mRNA levels in lung, intestine, kidney, brain, and liver. The highest TM mRNA levels were found in lung and the lowest in liver. Immunohistochemistry confirmed that TM was mainly localized on the endothelium of blood vessels and lymphatics. The alveolar capillaries of lung showed the strongest immunoreactivity, whereas the endothelium of hepatic sinusoids and cerebral cortex were virtually negative.  (+info)

Thrombomodulin is a protein that is found on the surface of endothelial cells, which line the interior surface of blood vessels. It plays an important role in the regulation of blood coagulation (clotting) and the activation of natural anticoagulant pathways. Thrombomodulin binds to thrombin, a protein involved in blood clotting, and changes its function from promoting coagulation to inhibiting it. This interaction also activates protein C, an important anticoagulant protein, which helps to prevent the excessive formation of blood clots. Thrombomodulin also has anti-inflammatory properties and is involved in the maintenance of the integrity of the endothelial cell lining.

Thrombin receptors are a type of G protein-coupled receptor (GPCR) that play a crucial role in hemostasis and thrombosis. They are activated by the protease thrombin, which is generated during the coagulation cascade. There are two main types of thrombin receptors: protease-activated receptor 1 (PAR-1) and PAR-4.

PAR-1 is expressed on various cell types including platelets, endothelial cells, and smooth muscle cells, while PAR-4 is primarily expressed on platelets. Activation of these receptors triggers a variety of intracellular signaling pathways that lead to diverse cellular responses such as platelet activation, aggregation, and secretion; vasoconstriction; and inflammation.

Dysregulation of thrombin receptor signaling has been implicated in several pathological conditions, including arterial and venous thrombosis, atherosclerosis, and cancer. Therefore, thrombin receptors are considered important therapeutic targets for the treatment of these disorders.

Protein C is a vitamin K-dependent protease that functions as an important regulator of coagulation and inflammation. It is a plasma protein produced in the liver that, when activated, degrades clotting factors Va and VIIIa to limit thrombus formation and prevent excessive blood clotting. Protein C also has anti-inflammatory properties by inhibiting the release of pro-inflammatory cytokines and reducing endothelial cell activation. Inherited or acquired deficiencies in Protein C can lead to an increased risk of thrombosis, a condition characterized by abnormal blood clot formation within blood vessels.

Thrombin is a serine protease enzyme that plays a crucial role in the coagulation cascade, which is a complex series of biochemical reactions that leads to the formation of a blood clot (thrombus) to prevent excessive bleeding during an injury. Thrombin is formed from its precursor protein, prothrombin, through a process called activation, which involves cleavage by another enzyme called factor Xa.

Once activated, thrombin converts fibrinogen, a soluble plasma protein, into fibrin, an insoluble protein that forms the structural framework of a blood clot. Thrombin also activates other components of the coagulation cascade, such as factor XIII, which crosslinks and stabilizes the fibrin network, and platelets, which contribute to the formation and growth of the clot.

Thrombin has several regulatory mechanisms that control its activity, including feedback inhibition by antithrombin III, a plasma protein that inactivates thrombin and other serine proteases, and tissue factor pathway inhibitor (TFPI), which inhibits the activation of factor Xa, thereby preventing further thrombin formation.

Overall, thrombin is an essential enzyme in hemostasis, the process that maintains the balance between bleeding and clotting in the body. However, excessive or uncontrolled thrombin activity can lead to pathological conditions such as thrombosis, atherosclerosis, and disseminated intravascular coagulation (DIC).

Carboxypeptidase U is also known as thiol protease or thiol carboxypeptidase. It is a type of enzyme that belongs to the peptidase family, specifically the serine proteases. This enzyme plays a role in the regulation of blood pressure by cleaving and inactivating bradykinin, a potent vasodilator peptide. Carboxypeptidase U is primarily produced in the kidneys and is released into the circulation in response to various stimuli, such as renin and angiotensin II. It functions by removing the C-terminal arginine residue from bradykinin, thereby reducing its biological activity and helping to maintain blood pressure homeostasis.

Cell surface receptors, also known as membrane receptors, are proteins located on the cell membrane that bind to specific molecules outside the cell, known as ligands. These receptors play a crucial role in signal transduction, which is the process of converting an extracellular signal into an intracellular response.

Cell surface receptors can be classified into several categories based on their structure and mechanism of action, including:

1. Ion channel receptors: These receptors contain a pore that opens to allow ions to flow across the cell membrane when they bind to their ligands. This ion flux can directly activate or inhibit various cellular processes.
2. G protein-coupled receptors (GPCRs): These receptors consist of seven transmembrane domains and are associated with heterotrimeric G proteins that modulate intracellular signaling pathways upon ligand binding.
3. Enzyme-linked receptors: These receptors possess an intrinsic enzymatic activity or are linked to an enzyme, which becomes activated when the receptor binds to its ligand. This activation can lead to the initiation of various signaling cascades within the cell.
4. Receptor tyrosine kinases (RTKs): These receptors contain intracellular tyrosine kinase domains that become activated upon ligand binding, leading to the phosphorylation and activation of downstream signaling molecules.
5. Integrins: These receptors are transmembrane proteins that mediate cell-cell or cell-matrix interactions by binding to extracellular matrix proteins or counter-receptors on adjacent cells. They play essential roles in cell adhesion, migration, and survival.

Cell surface receptors are involved in various physiological processes, including neurotransmission, hormone signaling, immune response, and cell growth and differentiation. Dysregulation of these receptors can contribute to the development of numerous diseases, such as cancer, diabetes, and neurological disorders.

Blood coagulation, also known as blood clotting, is a complex process that occurs in the body to prevent excessive bleeding when a blood vessel is damaged. This process involves several different proteins and chemical reactions that ultimately lead to the formation of a clot.

The coagulation cascade is initiated when blood comes into contact with tissue factor, which is exposed after damage to the blood vessel wall. This triggers a series of enzymatic reactions that activate clotting factors, leading to the formation of a fibrin clot. Fibrin is a protein that forms a mesh-like structure that traps platelets and red blood cells to form a stable clot.

Once the bleeding has stopped, the coagulation process is regulated and inhibited to prevent excessive clotting. The fibrinolytic system degrades the clot over time, allowing for the restoration of normal blood flow.

Abnormalities in the blood coagulation process can lead to bleeding disorders or thrombotic disorders such as deep vein thrombosis and pulmonary embolism.

The endothelium is a thin layer of simple squamous epithelial cells that lines the interior surface of blood vessels, lymphatic vessels, and heart chambers. The vascular endothelium, specifically, refers to the endothelial cells that line the blood vessels. These cells play a crucial role in maintaining vascular homeostasis by regulating vasomotor tone, coagulation, platelet activation, inflammation, and permeability of the vessel wall. They also contribute to the growth and repair of the vascular system and are involved in various pathological processes such as atherosclerosis, hypertension, and diabetes.

Thromboplastin is a substance that activates the coagulation cascade, leading to the formation of a clot (thrombus). It's primarily found in damaged or injured tissues and blood vessels, as well as in platelets (thrombocytes). There are two types of thromboplastin:

1. Extrinsic thromboplastin (also known as tissue factor): This is a transmembrane glycoprotein that is primarily found in subendothelial cells and released upon injury to the blood vessels. It initiates the extrinsic pathway of coagulation by binding to and activating Factor VII, ultimately leading to the formation of thrombin and fibrin clots.
2. Intrinsic thromboplastin (also known as plasma thromboplastin or factor III): This term is used less frequently and refers to a labile phospholipid component present in platelet membranes, which plays a role in the intrinsic pathway of coagulation.

In clinical settings, the term "thromboplastin" often refers to reagents used in laboratory tests like the prothrombin time (PT) and activated partial thromboplastin time (aPTT). These reagents contain a source of tissue factor and calcium ions to initiate and monitor the coagulation process.

Blood coagulation factors, also known as clotting factors, are a group of proteins that play a crucial role in the blood coagulation process. They are essential for maintaining hemostasis, which is the body's ability to stop bleeding after injury.

There are 13 known blood coagulation factors, and they are designated by Roman numerals I through XIII. These factors are produced in the liver and are normally present in an inactive form in the blood. When there is an injury to a blood vessel, the coagulation process is initiated, leading to the activation of these factors in a specific order.

The coagulation cascade involves two pathways: the intrinsic and extrinsic pathways. The intrinsic pathway is activated when there is damage to the blood vessel itself, while the extrinsic pathway is activated by tissue factor released from damaged tissues. Both pathways converge at the common pathway, leading to the formation of a fibrin clot.

Blood coagulation factors work together in a complex series of reactions that involve activation, binding, and proteolysis. When one factor is activated, it activates the next factor in the cascade, and so on. This process continues until a stable fibrin clot is formed.

Deficiencies or abnormalities in blood coagulation factors can lead to bleeding disorders such as hemophilia or thrombosis. Hemophilia is a genetic disorder that affects one or more of the coagulation factors, leading to excessive bleeding and difficulty forming clots. Thrombosis, on the other hand, occurs when there is an abnormal formation of blood clots in the blood vessels, which can lead to serious complications such as stroke or pulmonary embolism.

Antithrombin III is a protein that inhibits the formation of blood clots (thrombi) in the body. It does this by inactivating several enzymes involved in coagulation, including thrombin and factor Xa. Antithrombin III is produced naturally by the liver and is also available as a medication for the prevention and treatment of thromboembolic disorders, such as deep vein thrombosis and pulmonary embolism. It works by binding to and neutralizing excess clotting factors in the bloodstream, thereby reducing the risk of clot formation.

Hirudin is not a medical term itself, but it is a specific substance with medical relevance. Hirudin is a naturally occurring anticoagulant that is found in the saliva of certain species of leeches (such as Hirudo medicinalis). This compound works by inhibiting the activity of thrombin, a key enzyme in the coagulation cascade, which ultimately results in preventing blood clot formation.

Medically, hirudin has been used in some research and therapeutic settings for its anticoagulant properties. For instance, recombinant hirudin (also known as lepirudin) is available for clinical use as an injectable anticoagulant to treat or prevent blood clots in specific medical conditions, such as heparin-induced thrombocytopenia (HIT).

In summary, Hirudins are a group of anticoagulant substances, primarily derived from leeches, that inhibit the activity of thrombin and have potential medical applications in preventing or treating blood clots.

Hemostasis is the physiological process that occurs to stop bleeding (bleeding control) when a blood vessel is damaged. This involves the interaction of platelets, vasoconstriction, and blood clotting factors leading to the formation of a clot. The ultimate goal of hemostasis is to maintain the integrity of the vascular system while preventing excessive blood loss.

Disseminated Intravascular Coagulation (DIC) is a complex medical condition characterized by the abnormal activation of the coagulation cascade, leading to the formation of blood clots in small blood vessels throughout the body. This process can result in the consumption of clotting factors and platelets, which can then lead to bleeding complications. DIC can be caused by a variety of underlying conditions, including sepsis, trauma, cancer, and obstetric emergencies.

The term "disseminated" refers to the widespread nature of the clotting activation, while "intravascular" indicates that the clotting is occurring within the blood vessels. The condition can manifest as both bleeding and clotting complications, which can make it challenging to diagnose and manage.

The diagnosis of DIC typically involves laboratory tests that evaluate coagulation factors, platelet count, fibrin degradation products, and other markers of coagulation activation. Treatment is focused on addressing the underlying cause of the condition while also managing any bleeding or clotting complications that may arise.

Fibrinopeptide B is a small protein molecule that is cleaved and released from the larger fibrinogen protein during the blood clotting process, also known as coagulation. Fibrinogen is converted to fibrin by the action of thrombin, an enzyme that activates the coagulation cascade. Thrombin cuts specific peptide bonds in fibrinogen, releasing fibrinopeptides A and B from the resulting fibrin monomers.

The release of fibrinopeptide B is a critical step in the formation of a stable blood clot because it allows for the exposure of binding sites on the fibrin molecules that facilitate their polymerization into an insoluble network, trapping platelets and other components to form a clot. The measurement of fibrinopeptide B levels can be used as a marker for thrombin activity and fibrin formation in various clinical settings, such as monitoring the effectiveness of anticoagulant therapy or diagnosing conditions associated with abnormal blood clotting.

Prothrombin is a protein present in blood plasma, and it's also known as coagulation factor II. It plays a crucial role in the coagulation cascade, which is a complex series of reactions that leads to the formation of a blood clot.

When an injury occurs, the coagulation cascade is initiated to prevent excessive blood loss. Prothrombin is converted into its active form, thrombin, by another factor called factor Xa in the presence of calcium ions, phospholipids, and factor Va. Thrombin then catalyzes the conversion of fibrinogen into fibrin, forming a stable clot.

Prothrombin levels can be measured through a blood test, which is often used to diagnose or monitor conditions related to bleeding or coagulation disorders, such as liver disease or vitamin K deficiency.

The umbilical veins are blood vessels in the umbilical cord that carry oxygenated and nutrient-rich blood from the mother to the developing fetus during pregnancy. There are typically two umbilical veins, one of which usually degenerates and becomes obliterated, leaving a single functional vein. This remaining vein is known as the larger umbilical vein or the venous duct. It enters the fetal abdomen through the umbilicus and passes through the liver, where it branches off to form the portal sinus. Ultimately, the blood from the umbilical vein mixes with the blood from the inferior vena cava and is pumped to the heart through the right atrium.

It's important to note that after birth, the umbilical veins are no longer needed and undergo involution, becoming the ligamentum teres in the adult.

Fibrinogen is a soluble protein present in plasma, synthesized by the liver. It plays an essential role in blood coagulation. When an injury occurs, fibrinogen gets converted into insoluble fibrin by the action of thrombin, forming a fibrin clot that helps to stop bleeding from the injured site. Therefore, fibrinogen is crucial for hemostasis, which is the process of stopping bleeding and starting the healing process after an injury.

Thrombosis is the formation of a blood clot (thrombus) inside a blood vessel, obstructing the flow of blood through the circulatory system. When a clot forms in an artery, it can cut off the supply of oxygen and nutrients to the tissues served by that artery, leading to damage or tissue death. If a thrombus forms in the heart, it can cause a heart attack. If a thrombus breaks off and travels through the bloodstream, it can lodge in a smaller vessel, causing blockage and potentially leading to damage in the organ that the vessel supplies. This is known as an embolism.

Thrombosis can occur due to various factors such as injury to the blood vessel wall, abnormalities in blood flow, or changes in the composition of the blood. Certain medical conditions, medications, and lifestyle factors can increase the risk of thrombosis. Treatment typically involves anticoagulant or thrombolytic therapy to dissolve or prevent further growth of the clot, as well as addressing any underlying causes.

Von Willebrand factor (vWF) is a large multimeric glycoprotein that plays a crucial role in hemostasis, the process which leads to the cessation of bleeding and the formation of a blood clot. It was named after Erik Adolf von Willebrand, a Finnish physician who first described the disorder associated with its deficiency, known as von Willebrand disease (vWD).

The primary functions of vWF include:

1. Platelet adhesion and aggregation: vWF mediates the initial attachment of platelets to damaged blood vessel walls by binding to exposed collagen fibers and then interacting with glycoprotein Ib (GPIb) receptors on the surface of platelets, facilitating platelet adhesion. Subsequently, vWF also promotes platelet-platelet interactions (aggregation) through its interaction with platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptors under high shear stress conditions found in areas of turbulent blood flow, such as arterioles and the capillary bed.

2. Transport and stabilization of coagulation factor VIII: vWF serves as a carrier protein for coagulation factor VIII (FVIII), protecting it from proteolytic degradation and maintaining its stability in circulation. This interaction between vWF and FVIII is essential for the proper functioning of the coagulation cascade, particularly in the context of vWD, where impaired FVIII function can lead to bleeding disorders.

3. Wound healing: vWF contributes to wound healing by promoting platelet adhesion and aggregation at the site of injury, which facilitates the formation of a provisional fibrin-based clot that serves as a scaffold for tissue repair and regeneration.

In summary, von Willebrand factor is a vital hemostatic protein involved in platelet adhesion, aggregation, coagulation factor VIII stabilization, and wound healing. Deficiencies or dysfunctions in vWF can lead to bleeding disorders such as von Willebrand disease.

Recombinant proteins are artificially created proteins produced through the use of recombinant DNA technology. This process involves combining DNA molecules from different sources to create a new set of genes that encode for a specific protein. The resulting recombinant protein can then be expressed, purified, and used for various applications in research, medicine, and industry.

Recombinant proteins are widely used in biomedical research to study protein function, structure, and interactions. They are also used in the development of diagnostic tests, vaccines, and therapeutic drugs. For example, recombinant insulin is a common treatment for diabetes, while recombinant human growth hormone is used to treat growth disorders.

The production of recombinant proteins typically involves the use of host cells, such as bacteria, yeast, or mammalian cells, which are engineered to express the desired protein. The host cells are transformed with a plasmid vector containing the gene of interest, along with regulatory elements that control its expression. Once the host cells are cultured and the protein is expressed, it can be purified using various chromatography techniques.

Overall, recombinant proteins have revolutionized many areas of biology and medicine, enabling researchers to study and manipulate proteins in ways that were previously impossible.

Fibrinopeptide A is a small protein molecule that is cleaved and released from the larger fibrinogen protein during the blood clotting process. Specifically, it is removed by the enzyme thrombin as part of the conversion of fibrinogen to fibrin, which is the main structural component of a blood clot. The measurement of Fibrinopeptide A in the blood can be used as a marker for ongoing thrombin activation and fibrin formation, which are key events in coagulation and hemostasis. Increased levels of Fibrinopeptide A may indicate abnormal or excessive blood clotting, such as in disseminated intravascular coagulation (DIC) or deep vein thrombosis (DVT).

Factor V, also known as proaccelerin or labile factor, is a protein involved in the coagulation cascade, which is a series of chemical reactions that leads to the formation of a blood clot. Factor V acts as a cofactor for the activation of Factor X to Factor Xa, which is a critical step in the coagulation cascade.

When blood vessels are damaged, the coagulation cascade is initiated to prevent excessive bleeding. During this process, Factor V is activated by thrombin, another protein involved in coagulation, and then forms a complex with activated Factor X and calcium ions on the surface of platelets or other cells. This complex converts prothrombin to thrombin, which then converts fibrinogen to fibrin to form a stable clot.

Deficiency or dysfunction of Factor V can lead to bleeding disorders such as hemophilia B or factor V deficiency, while mutations in the gene encoding Factor V can increase the risk of thrombosis, as seen in the Factor V Leiden mutation.

Fibrinolysis is the natural process in the body that leads to the dissolution of blood clots. It is a vital part of hemostasis, the process that regulates bleeding and wound healing. Fibrinolysis occurs when plasminogen activators convert plasminogen to plasmin, an enzyme that breaks down fibrin, the insoluble protein mesh that forms the structure of a blood clot. This process helps to prevent excessive clotting and maintains the fluidity of the blood. In medical settings, fibrinolysis can also refer to the therapeutic use of drugs that stimulate this process to dissolve unwanted or harmful blood clots, such as those that cause deep vein thrombosis or pulmonary embolism.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

Factor V, also known as proaccelerin or labile factor, is a protein involved in the coagulation cascade, which is a series of chemical reactions that leads to the formation of a blood clot. Factor V acts as a cofactor for the conversion of prothrombin to thrombin, which is a critical step in the coagulation process.

Inherited deficiencies or abnormalities in Factor V can lead to bleeding disorders. For example, Factor V Leiden is a genetic mutation that causes an increased risk of blood clots, while Factor V deficiency can cause a bleeding disorder.

It's worth noting that "Factor Va" is not a standard medical term. Factor V becomes activated and turns into Factor Va during the coagulation cascade. Therefore, it is possible that you are looking for the definition of "Factor Va" in the context of its role as an activated form of Factor V in the coagulation process.

Chondroitin lyases are a group of enzymes that breakdown chondroitin, which is a type of proteoglycan found in connective tissues such as cartilage. These enzymes cleave chondroitin at specific points by removing certain sugar units, thereby breaking down the large, complex molecule into smaller fragments. Chondroitin lyases are classified based on their site of action and the type of fragment they produce. They play important roles in various biological processes, including tissue remodeling, growth, and development. In some cases, chondroitin lyases may also be used in research and medical settings to study the structure and function of proteoglycans or for the production of smaller chondroitin fragments with therapeutic potential.

The endothelium is the thin, delicate tissue that lines the interior surface of blood vessels and lymphatic vessels. It is a single layer of cells called endothelial cells that are in contact with the blood or lymph fluid. The endothelium plays an essential role in maintaining vascular homeostasis by regulating blood flow, coagulation, platelet activation, immune function, and angiogenesis (the formation of new blood vessels). It also acts as a barrier between the vessel wall and the circulating blood or lymph fluid. Dysfunction of the endothelium has been implicated in various cardiovascular diseases, diabetes, inflammation, and cancer.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

A hemangioma is a benign (noncancerous) vascular tumor or growth that originates from blood vessels. It is characterized by an overgrowth of endothelial cells, which line the interior surface of blood vessels. Hemangiomas can occur in various parts of the body, but they are most commonly found on the skin and mucous membranes.

Hemangiomas can be classified into two main types:

1. Capillary hemangioma (also known as strawberry hemangioma): This type is more common and typically appears during the first few weeks of life. It grows rapidly for several months before gradually involuting (or shrinking) on its own, usually within the first 5 years of life. Capillary hemangiomas can be superficial, appearing as a bright red, raised lesion on the skin, or deep, forming a bluish, compressible mass beneath the skin.

2. Cavernous hemangioma: This type is less common and typically appears during infancy or early childhood. It consists of large, dilated blood vessels and can occur in various organs, including the skin, liver, brain, and gastrointestinal tract. Cavernous hemangiomas on the skin appear as a rubbery, bluish mass that does not typically involute like capillary hemangiomas.

Most hemangiomas do not require treatment, especially if they are small and not causing any significant problems. However, in cases where hemangiomas interfere with vital functions, impair vision or hearing, or become infected, various treatments may be considered, such as medication (e.g., corticosteroids, propranolol), laser therapy, surgical excision, or embolization.

Carboxypeptidase B is a type of enzyme that belongs to the peptidase family. It is also known as carboxypeptidase B1 or CpB. This enzyme plays a crucial role in the digestion of proteins by cleaving specific amino acids from the carboxyl-terminal end of polypeptides.

Carboxypeptidase B preferentially removes basic arginine and lysine residues from protein substrates, making it an essential enzyme in various physiological processes, including blood clotting, hormone processing, and neuropeptide metabolism. It is synthesized as an inactive zymogen, procarboxypeptidase B, which is converted to its active form upon proteolytic activation.

In addition to its physiological functions, carboxypeptidase B has applications in research and industry, such as protein sequencing, peptide synthesis, and food processing.

An encyclopedia is a comprehensive reference work containing articles on various topics, usually arranged in alphabetical order. In the context of medicine, a medical encyclopedia is a collection of articles that provide information about a wide range of medical topics, including diseases and conditions, treatments, tests, procedures, and anatomy and physiology. Medical encyclopedias may be published in print or electronic formats and are often used as a starting point for researching medical topics. They can provide reliable and accurate information on medical subjects, making them useful resources for healthcare professionals, students, and patients alike. Some well-known examples of medical encyclopedias include the Merck Manual and the Stedman's Medical Dictionary.

... is also expressed on human mesothelial cell, monocyte and a dendritic cell subset. In humans, thrombomodulin is ... Thrombomodulin (TM), CD141 or BDCA-3 is an integral membrane protein expressed on the surface of endothelial cells and serves ... Thrombomodulin functions as a cofactor in the thrombin-induced activation of protein C in the anticoagulant pathway by forming ... IPR001491 Thrombomodulin Accessed January 19, 2012. Verhagen HJ, Heijnen-Snyder GJ, Pronk A, Vroom TM, van Vroonhoven TJ, ...
... bound to thrombomodulin activates protein C, an inhibitor of the coagulation cascade. The activation of protein C is ... Thrombin interacts with thrombomodulin. As part of its activity in the coagulation cascade, thrombin also promotes platelet ... Esmon CT (July 1995). "Thrombomodulin as a model of molecular mechanisms that modulate protease specificity and function at the ... However, binding of the active fragment of thrombomodulin appears to allosterically promote the active conformation of thrombin ...
Lohi O, Urban S, Freeman M (February 2004). "Diverse substrate recognition mechanisms for rhomboids; thrombomodulin is cleaved ... December 2011). "Functions of rhomboid family protease RHBDL2 and thrombomodulin in wound healing". The Journal of ... the cleavage of the anticoagulant protein thrombomodulin and wound healing. All eukaryotes have a mitochondrial rhomboid. In ...
... the protein may be said to be activated not by thrombin but the thrombin-thrombomodulin (or even thrombin-thrombomodulin-EPCR) ... The activation of protein C is strongly promoted by thrombomodulin and endothelial protein C receptor (EPCR), the latter of ... Another is necessary for interacting with thrombomodulin.: 2833 Post-translational modifications. Human Protein C has at least ... domain of thrombomodulin, reducing the Michaelis constant (KM) for their reaction.: 2386 : 29S In addition, Protein C is ...
Known substrates of RHBDL2 include thrombomodulin and epidermal growth factor; profiling of the substrate repertoire of RHBDL2 ... December 2011). "Functions of rhomboid family protease RHBDL2 and thrombomodulin in wound healing". The Journal of ...
When this occurs, endothelial cells downregulate substances such as thrombomodulin, which is a key modulator of thrombin ... Ito, Takashi; Kakihana, Yasuyuki; Maruyama, Ikuro (2016-01-01). "Thrombomodulin as an intravascular safeguard against ...
Van de Wouwer M, Collen D, Conway EM (2005). "Thrombomodulin-protein C-EPCR system: integrated to regulate coagulation and ...
The second ligand is a fragment of thrombomodulin exerting anti-inflammatory function in mice. Human GPR15 was originally ... April 2017). "G-protein coupled receptor 15 mediates angiogenesis and cytoprotective function of thrombomodulin". Scientific ...
2003). "Modulation of procarboxypeptidase R (ProCPR) activation by complementary peptides to thrombomodulin". Microbiol. ...
RHBDL2 cleaves thrombomodulin at the transmembrane domain and causes the release of soluble thrombomodulin. RHBDF2 may also ... Thrombomodulin - a membrane glycoprotein - is upregulated in neoepidermis during cutaneous wound healing. ...
... suggested to be comparable to amifostine Thrombomodulin Activated protein C Chelation therapy, a countermeasure for treating ... "Pharmacological targeting of the thrombomodulin-activated protein C pathway mitigates radiation toxicity". Nature Medicine. 18 ...
Other proteins contain only cEGF such as thrombomodulin and the LDL-receptor. In mixed EGF-proteins the hEGF- and cEGF-like ... "beta-Hydroxyaspartic acid or beta-hydroxyasparagine in bovine low density lipoprotein receptor and in bovine thrombomodulin". ...
In the presence of thrombomodulin, thrombin acts to decrease clotting by activating protein C; therefore, the concentration and ...
Defects in interaction with thrombomodulin, phospholipids, factors V/VIII and others have been described. The majority of ...
Mosnier LO, Elisen MG, Bouma BN, Meijers JC (2002). "Protein C inhibitor regulates the thrombin-thrombomodulin complex in the ... When it is activated by proteolysis at residue Arg92 by the thrombin/thrombomodulin complex, CPB2 exhibits carboxypeptidase ... do not determine the thrombomodulin dependence of TAFI activation". J. Biol. Chem. 277 (12): 9944-51. doi:10.1074/jbc. ... couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex". J. Biol. Chem. 271 (28): 16603- ...
This family comprise three other members, CLEC14A, CD93 and Thrombomodulin the latter of which are better characterized. The ...
Thrombomodulin binds these proteins in such a way that it activates Protein C. The activated form, along with protein S and a ... Protein C is activated in a sequence that starts with Protein C and thrombin binding to a cell surface protein thrombomodulin. ... in the presence of thrombomodulin). By activating Factor XIII, covalent bonds are formed that crosslink the fibrin polymers ...
... including reduced synthesis of anticoagulation factors such as tissue factor pathway inhibitor and thrombomodulin. The effects ...
Substances such as antithrombin III, thrombomodulin, tissue-type plasminogen activator and urokinase dissolve formed blood ...
The endothelial cells of intact vessels prevent blood clotting with a heparin-like molecule and thrombomodulin, and prevent ...
CLEC14A and thrombomodulin, a well characterized anticoagulant. All of them contain a C-type lectin domain, a series of ... CD93 has been suggested to have arisen from the thrombomodulin gene through a duplication event. CD93 was originally identified ...
Later, mutations in complement factor H, complement factor I, membrane cofactor protein, factor B, C3, and thrombomodulin have ...
... thrombomodulin - thromboxane receptor - thylakoid - thyroid hormone receptor - thyrotropin - thyrotropin receptor - thyrotropin ...
... autoimmune Thrombocytosis Thrombomodulin anomalies, familial Thrombotic microangiopathy, familial Thrush Thumb absence ...
Recombinant human thrombomodulin (rhTM) This disambiguation page lists articles associated with the title RHTM. If an internal ...
Thrombostat thrombomodulin alfa (INN) thymalfasin (INN) thymocartin (INN) thymoctonan (INN) thymopentin (INN) thymostimulin ( ...
... and thrombomodulin). This results in platelet activation, damage to endothelial cells (cells that line the blood vessels), and ...
... thrombomodulin) and NOS3 (endothelial nitric oxide synthase) expression, having an anti-thrombotic effect Through the ...
... nocturnal hemoglobinuria Ficolin 3 deficiency Properdin deficiency Factor I deficiency Factor H deficiency Thrombomodulin ...
... thrombomodulin MeSH D12.776.395.550.625.905 - p-selectin MeSH D12.776.395.550.895.800 - thrombospondin 1 MeSH D12.776.395.560. ...
Thrombomodulin is also expressed on human mesothelial cell, monocyte and a dendritic cell subset. In humans, thrombomodulin is ... Thrombomodulin (TM), CD141 or BDCA-3 is an integral membrane protein expressed on the surface of endothelial cells and serves ... Thrombomodulin functions as a cofactor in the thrombin-induced activation of protein C in the anticoagulant pathway by forming ... IPR001491 Thrombomodulin Accessed January 19, 2012. Verhagen HJ, Heijnen-Snyder GJ, Pronk A, Vroom TM, van Vroonhoven TJ, ...
... type I membrane glycoprotein also known as thrombomodulin, TM, THRM, THBD, and fetomodulin. CD141 is an important cofactor in ... Brilliant Violet 421™ anti-human CD141 (Thrombomodulin). M80. FC. Brilliant Violet 785™ anti-human CD141 (Thrombomodulin). M80 ... Thrombomodulin, TM, THRM, THBD, Fetomodulin, BDCA-3 Isotype Mouse IgG1, κ Barcode Sequence GGATAACCGCGCTTT Ave. Rating Submit a ... CD141 is a 75 kD, single chain, type I membrane glycoprotein also known as thrombomodulin, TM, THRM, THBD, and fetomodulin. ...
Genetics of the thrombomodulin-endothelial cell protein C receptor system and the risk of early-onset ischemic stroke. *Mark ... Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin-protein C ... Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin-protein C ... Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin-protein C ...
... experiments on the thrombin-thrombomodulin (TM) complex. Thrombin promotes procoagulative fibrinogen cleavage when fibrinogen ... experiments on the thrombin-thrombomodulin (TM) complex. Thrombin promotes procoagulative fibrinogen cleavage when fibrinogen ...
... recombinant and soluble thrombomodulin (ART-123). It is a human protein with both thrombin inhibiting and protein C stimulating ... Thrombomodulin Alfa is a novel, recombinant and soluble thrombomodulin (ART-123). It is a human protein with both thrombin ... Bound to thrombin, Thrombomodulin alfa inhibits its procoagulant activity and promotes activation of protein C. Thrombomodulin ... Thrombomodulin alfa is a soluble form of recombinant human thrombomodulin comprising all extracellular domains of ...
Thrombomodulin-related bleeding disorder. Synonyms: THBD-related bleeding disorder , THBD-related coagulopathy , Thrombomodulin ... Thrombomodulin-related bleeding disorder?. Our RARE Concierge Services Guides are available to assist you by providing ... Thrombomodulin-related bleeding disorder. Get in touch with RARE Concierge.. Contact RARE Concierge ... Abnormal laboratory findings include markedly elevated plasma thrombomodulin reduced prothrombin consumption and decreased ...
How Thrombomodulin Enables W215A/E217A Thrombin to Cleave Protein C but Not Fibrinogen. Title: How Thrombomodulin Enables W215A ... Thrombomodulin (THBD) gene variants and thrombotic risk in a population-based cohort study. Title: Thrombomodulin (THBD) gene ... CLECT_thrombomodulin_like; C-type lectin-like domain (CTLD) of the type found in human thrombomodulin(TM), Endosialin, C14orf27 ... Plasma Thrombomodulin Levels and Ischemic Stroke: A Population-Based Prognostic Cohort Study. Title: Plasma Thrombomodulin ...
baboon - complement-regulatory proteins - costimulation blockade - heart - pig - thrombomodulin - thrombotic microangiopathy - ... expressed human thrombomodulin (TBM). Immunosuppression included anti-thymocyte globulin with anti-CD154mAb (Regimen 1: n=2) or ... expressed human thrombomodulin (TBM). Immunosuppression included anti-thymocyte globulin with anti-CD154mAb (Regimen 1: n=2) or ... exploratory preliminary experience with pigs transgenic for human thrombomodulin and comparison of three costimulation blockade ...
Dendritic cells (DCs) bridge the connection between innate and adaptive immunity. DCs present antigens to T cells and stimulate potent cytotoxic T-cell responses. Metabolic reprogramming is critical for DC development and activation; however, metabolic adaptations and regulation in DC subsets remain …
... thrombomodulin; t-PA = tissue type plasminogen activator; u-PA = urokinase plasminogen activator; XL= crosslinked. ...
5) Increases in soluble thrombomodulin and EPCR likely leave less surface bound forms, inhibiting the ability of endothelial ... 2) Endothelial surface bound thrombomodulin and EPCR lead to activation of protein C; PAR-1 activation strengthens endothelial ...
Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin-protein C ... Genetics of the thrombomodulin-endothelial cell protein C receptor system and the risk of early-onset ischemic stroke ... Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin-protein C ... Genetics of the thrombomodulin-endothelial cell protein C receptor system and the risk of early-onset ischemic stroke. PloS one ...
Mouse TM (Thrombomodulin) CLIA Kit , G-EC-01664 MSRP: Was: Now: $266.00 - $4,134.00 ...
Endothelial thrombomodulin downregulation caused by hypoxia contributes to severe infiltration and coagulopathy in COVID-19 ... Endothelial thrombomodulin downregulation caused by hypoxia contributes to severe infiltration and coagulopathy in COVID-19 ...
Idiopathic pulmonary fibrosis Acute exacerbation Recombinant human thrombomodulin α Hypercoagulability Received 23 Jun 2015 / ... Recombinant human thrombomodulin α has the possibility of improving prognosis in acute exacerbation of idiopathic pulmonary ... We studied the efficacy of recombinant human thrombomodulin (rhTM) α for acute exacerbation of idiopathic pulmonary fibrosis. ... Efficacy of recombinant human thrombomodulin α in acute exacerbation of idiopathic pulmonary fibrosis ...
Downregulation of Thrombomodulin-Thrombin-Activated Protein C pathway as a mechanism for SARS-CoV-2 induced endotheliopathy and ... Agarwal S, Jacobi P, Sartain S. Downregulation of Thrombomodulin-Thrombin-Activated Protein C pathway as a mechanism for SARS- ... Thrombomodulin (TM) is an endothelial glycoprotein that plays a crucial role as a natural anticoagulant, binding thrombin to ... abstracts.isth.org/abstract/downregulation-of-thrombomodulin-thrombin-activated-protein-c-pathway-as-a-mechanism-for-sars-cov-2 ...
Knockdown of thrombomodulin enhances HCC cell migration through increase of ZEB1 and decrease of E-cadherin gene expression. ... Knockdown of thrombomodulin enhances HCC cell migration through increase of ZEB1 and decrease of E-cadherin gene expression. / ... Knockdown of thrombomodulin enhances HCC cell migration through increase of ZEB1 and decrease of E-cadherin gene expression. In ... Knockdown of thrombomodulin enhances HCC cell migration through increase of ZEB1 and decrease of E-cadherin gene expression. ...
Novel Sepsis Phenotypes, Effect of Thrombomodulin on Mortality in Sepsis-Associated Coagulopathy, Effect of Laparoscopic vs ...
Matsuo, S., Ikeda, T., Ikeda, K. et al. Comparison of the effects of recombinant human soluble thrombomodulin for systemic ... Recombinant human soluble thrombomodulin (rhs-TM) has a potent anticoagulant effect on septic disseminated intravascular ... Comparison of the effects of recombinant human soluble thrombomodulin for systemic inflammatory response syndrome-associated ... Comparison of the effects of recombinant human soluble thrombomodulin for systemic inflammatory response syndrome-associated ...
Known substrates of RHBDL2 include thrombomodulin and epidermal growth factor; profiling of the substrate repertoire of RHBDL2 ... December 2011). "Functions of rhomboid family protease RHBDL2 and thrombomodulin in wound healing". The Journal of ...
The NLR was negatively predicted by RAGE in addition to IL4 and positively predicted by thrombomodulin and procalcitonin. ...
Thrombin, in turn, converts fibrinogen to fibrin; activates soluble FV, FVIII, FXI, and FXIII; and binds to thrombomodulin to ...
Exploring traditional and nontraditional roles for thrombomodulin. Blood. (2018) 132:148-58. doi: 10.1182/blood-2017-12-768994 ... The binding of thrombin to endothelial-bound thrombomodulin, in addition, activates the anticoagulant pathway of protein C (17 ...
Thrombomodulin and protein C are members of an endogenous anticoagulant system. Thrombin complexed with thrombomodulin loses ...
Malignant cells are positive for CK7, CK20, p63, thrombomodulin, and GATA3. Many tumors are also positive for uroplakin III. ... By immunohistochemistry, benign Brenner tumors are positive for CK7, p63, GATA3, uroplakin III, and thrombomodulin. CK20 is ...
ART-123 is a recombinant, soluble thrombomodulin. A regulatory submission for approval of ART-123 in the treatment of DIC has ...
... or thrombomodulin (THBD). The gene expression regulated by KLF4 overlaps with that regulated by KLF2. The protective roles of ...
Thrombomodulin Positive, specific and sensitive marker for mesothelial cells. Human [28] Vimentin Help in identifying ...
  • Thrombomodulin Alfa is a novel, recombinant and soluble thrombomodulin (ART-123). (drugbank.com)
  • Kearon C, Comp P, Douketis J, Royds R, Yamada K, Gent M: Dose-response study of recombinant human soluble thrombomodulin (ART-123) in the prevention of venous thromboembolism after total hip replacement. (drugbank.com)
  • A rare genetic coagulation disorder characterized by marked bleeding tendency and posttraumatic bleeding with easy bruising soft tissue and muscle bleeding hemarthroses and menorrhagia due to an increase of soluble thrombomodulin in plasma with subsequent protein C activation and reduction of thrombin generation within a potential thrombus. (globalgenes.org)
  • 5) Increases in soluble thrombomodulin and EPCR likely leave less surface bound forms, inhibiting the ability of endothelial cells to activate cytoprotective pathways through PAR-1 and increasing their susceptibility to immune mediated destruction. (cdc.gov)
  • Recombinant human soluble thrombomodulin (rhs-TM) has a potent anticoagulant effect on septic disseminated intravascular coagulation (DIC) by binding to thrombin and activating protein C. The infusion dosage of rhs-TM should be reduced for patients with renal failure. (biomedcentral.com)
  • Diabetic nephropathy (DN) is a leading selectin), and soluble thrombomodulin--are cause of chronic renal failure and is a grow- providing further evidence of the relation- ing concern given the increasing incidence ship between endothelial cell activation and of type 2 diabetes. (who.int)
  • In humans, thrombomodulin is encoded by the THBD gene. (wikipedia.org)
  • citation needed] Thrombomodulin is a glycoprotein on the surface of endothelial cells that, in addition to binding thrombin, regulates C3b inactivation by factor I. Mutations in the thrombomodulin gene (THBD) have also been reported to be associated with atypical hemolytic-uremic syndrome (aHUS). (wikipedia.org)
  • Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin-protein C system (THBD and PROCR) may similarly be associated with early-onset ischemic stroke. (lu.se)
  • Thrombomodulin alfa is a soluble form of recombinant human thrombomodulin comprising all extracellular domains of thrombomodulin. (drugbank.com)
  • We studied the efficacy of recombinant human thrombomodulin (rhTM) α for acute exacerbation of idiopathic pulmonary fibrosis. (or.jp)
  • Recombinant human thrombomodulin α has the possibility of improving prognosis in acute exacerbation of idiopathic pulmonary fibrosis. (or.jp)
  • A missense mutation in lectin domain of thrombomodulin causing functional deficiency. (nih.gov)
  • Thrombomodulin (TM), CD141 or BDCA-3 is an integral membrane protein expressed on the surface of endothelial cells and serves as a cofactor for thrombin. (wikipedia.org)
  • Bound to thrombin, Thrombomodulin alfa inhibits its procoagulant activity and promotes activation of protein C. Thrombomodulin alfa inhibits thrombin generation by the activation of protein C and the subsequent inactivation of factor Va in the presence of protein S. Thrombomodulin alfa attenuates the extension of the clot by inhibiting further thrombin generation on clots, while other anticoagulants inhibit the initiation of clot formation. (drugbank.com)
  • A higher concentration of Thrombomodulin alfa is needed to affect clotting time and platelet aggregation than thrombin generation. (drugbank.com)
  • Abnormal laboratory findings include markedly elevated plasma thrombomodulin reduced prothrombin consumption and decreased thrombin generation. (globalgenes.org)
  • Background: Thrombomodulin (TM) is a key molecule mediating circulation homeostasis through its binding to thrombin. (tmu.edu.tw)
  • Thrombomodulin (TM) is an endothelial glycoprotein that plays a crucial role as a natural anticoagulant, binding thrombin to activate protein C (PC). (isth.org)
  • Thrombomodulin (TM) alfa, a recombinant human soluble TM, enhances activation of pro-carboxypeptidase B2 (pro-CPB2) by thrombin. (drugbank.com)
  • Association of SNP (rs1042579) in thrombomodulin gene and plasma thrombomodulin level in North Indian children with Kawasaki disease. (nih.gov)
  • Thrombomodulin-bound thrombin has procoagulant effect at the same time by inhibiting fibrinolysis by cleaving thrombin-activatable fibrinolysis inhibitor (TAFI, aka carboxypeptidase B2) into its active form. (wikipedia.org)
  • Tawara S, Sakai T, Matsuzaki O: Anti-inflammatory and anti-fibrinolytic effects of thrombomodulin alfa through carboxypeptidase B2 in the presence of thrombin. (drugbank.com)
  • Carboxypeptidase B2 (CPB2) is released into the circulation as a proenzyme which is activated by the THROMBIN-THROMBOMODULIN complex. (bvsalud.org)
  • Thrombomodulin functions as a cofactor in the thrombin-induced activation of protein C in the anticoagulant pathway by forming a 1:1 stoichiometric complex with thrombin. (wikipedia.org)
  • Aberrant promoter hypermethylation regulates thrombomodulin in high altitude induced deep vein thrombosis. (nih.gov)
  • Thrombomodulin is also expressed on human mesothelial cell, monocyte and a dendritic cell subset. (wikipedia.org)
  • Matsusaki M, Omichi M, Maruyama I, Akashi M: Physical adsorption of human thrombomodulin (ART-123) onto polymeric biomaterials for developing an antithrombogenic blood-contacting material. (drugbank.com)
  • Hearts transplanted into Group A baboons (n=4) expressed additional CD55, and those into Group B (n=3) expressed human thrombomodulin (TBM). (unict.it)
  • Role of the lectin-like domain of thrombomodulin in septic cardiomyopathy. (nih.gov)
  • Activated protein C (APC) is the enzymatically active form of protein C after proteolytic cleavage by thrombomodulin-bound thrombin. (medscape.com)
  • We present nuclear magnetic resonance (NMR) and hydrogen deuterium exchange mass spectrometry (HDX-MS) experiments on the thrombin-thrombomodulin (TM) complex. (escholarship.org)
  • The isolated protein was activated by thrombin/thrombomodulin complex and further purified. (rndsystems.com)
  • Plasma Thrombomodulin Levels and Ischemic Stroke: A Population-Based Prognostic Cohort Study. (nih.gov)
  • Genetics of the thrombomodulin-endothelial cell protein C receptor sys" by John W. Cole, Huichun Xu et al. (aku.edu)
  • Recombinant human soluble thrombomodulin (rhTM) forms a complex with thrombin to inactivate coagulation. (nih.gov)
  • Since 2008, recombinant human soluble thrombomodulin (rTM) has been used to treat disseminated intravascular coagulation in Japan. (haematologica.org)
  • Rabbit Soluble thrombomodulin ELISA kit is suitable for detecting samples from rabbit species. (elisakit.cc)
  • 5) Increases in soluble thrombomodulin and EPCR likely leave less surface bound forms, inhibiting the ability of endothelial cells to activate cytoprotective pathways through PAR-1 and increasing their susceptibility to immune mediated destruction. (cdc.gov)
  • soluble thrombomodulin (sTM). (emedicinehealth.com)
  • The purpose of this study is to determine if objective serum tests, such as levels of soluble thrombomodulin (sTM) and soluble intercellular adhesion molecule-1 (sICAM-1), may be used in the diagnosis and staging of HAVS. (cdc.gov)
  • The encoded protein is cleaved to its activated form by the thrombin-thrombomodulin complex. (nih.gov)
  • A similar trend was observed in the level of thrombomodulin. (who.int)
  • Elevated lavels of soluble tumour necrosis factor receptor 1, thrombomodulin and soluble endothelial cell adhesion molecules in patients with dengue haemorrhagic fever. (who.int)
  • Thrombomodulin an endothelial cell surface glycoprotein act as a co-factor for thrombin catalyzed activation of protein C. activated protein C inhibits coagulation by inactivation the coagulation factor Va and VIIIa. (ginekologiaipoloznictwo.com)
  • 12. Transgenic Expression of Human Thrombomodulin Inhibits HMGB1-Induced Porcine Aortic Endothelial Cell Activation. (nih.gov)
  • Our study found that there was high significant difference (p≤0.01) between pre-eclampsia patients and healthy control group regarding serum thrombomodulin protein level and serum thrombomodulin protein increases significantly with mild and severe preeclampsia and HELLP syndrome and considered a good marker for evaluation of hypertensive patients with pregnancy. (ginekologiaipoloznictwo.com)
  • Serum thrombomodulin protein level is considered a good marker for evaluation of hypertensive patients with pregnancy. (ginekologiaipoloznictwo.com)
  • Serum thrombomodulin (sTM) concentration, a marker for the endothelium, is increased by endothelial damage or by decreased renal clearance. (nii.ac.jp)
  • Thrombomodulin (TM), CD141 or BDCA-3 is an integral membrane protein expressed on the surface of endothelial cells and serves as a cofactor for thrombin. (wikipedia.org)
  • Thrombomodulin functions as a cofactor in the thrombin-induced activation of protein C in the anticoagulant pathway by forming a 1:1 stoichiometric complex with thrombin. (wikipedia.org)
  • In addition to its multiple procoagulant roles, thrombin also acts as an anticoagulant when combined with the cofactor thrombomodulin in the protein Case complex. (hindawi.com)
  • The malignant mesothelioma (MM) is often complicated by thromboembolic episodes, with thrombomodulin (TM) playing a role in the anti-coagulant process. (nih.gov)
  • To determine the safety and efficacy of recombinant thrombomodulin (ART-123) in patients with suspected sepsis-associated disseminated intravascular coagulation. (medscape.com)
  • Mathematical model of the blood coagulation cascade including meizothrombin, protein C, thrombomodulin, factor VIIIa fragments, partially proteolyzed factor Va species and inactive factor Va fragments. (ebi.ac.uk)
  • Inhibitory effects of clone 1 on thrombomodulin-dependent TAFI activation were confirmed in clot lysis assays: Clone 1 fully attenuated TAFI activation in a dose-dependent manner when thrombomodulin was present, but not in its absence. (isth.org)
  • To develop variable domain of heavy-chain-only antibody (VhH) clones that inhibit TAFI activation by targeting human thrombomodulin. (isth.org)
  • In a microfluidic fibrinolysis model in which recalcified whole blood was perfused over a collagen, tissue factor and thrombomodulin surface in the presence of tissue plasminogen activator, clone 1 fully prevented TAFI activation. (isth.org)
  • Thrombin-thrombomodulin also activates thrombin-activatable fibrinolysis inhibitor (TAFI) that slows down fibrin degradation by plasmin. (hindawi.com)
  • Activation of TAFI is most effectively done in complex with thrombomodulin (TM). (uwo.ca)
  • To mitigate against these effects, we propose to derive triple transgenic animals over-expressing two human natural anticoagulants (called tissue factor pathway inhibitor and thrombomodulin) and the thromboregulatory factor CD39, which was found by the Applicant to profoundly inhibit the activation of platelets irrespective of the species of origin. (rotrf.org)
  • Circulating concentrations of soluble (s)L- and sE-selectins (sL-, sE-selectins), vascular and intercellular adhesion molecules (sVCAM-1, sICAM-1), pro/antiinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL-10)], tissue factor (sTF), thrombomodulin (sTM) and D-dimers (D-D) were assessed by enzyme immunoassay. (biomedcentral.com)
  • Targeting senescent hepatocytes using the thrombomodulin-PAR1 inhibitor vorapaxar ameliorates NAFLD progression. (bvsalud.org)
  • We previously found that the fifth epidermal growth factor-like domain of thrombomodulin (TME5) exerts cytoprotective and pro-angiogenic functions via G-protein coupled receptor 15 (GPR15). (haematologica.org)
  • We have demonstrated that exposure of bovine and human endothelial cells to TNF leads to suppression of the functional cell surface thrombin receptor, thrombomodulin (TM), and TM mRNA of virtually identical magnitude. (qxmd.com)
  • [ 6 ] ART-123 (Artisan Pharma, Waltham, MA) is a soluble recombinant human thrombomodulin that acts by reducing thrombin-mediated clotting and enhancing protein C activation at the site of clotting. (medscape.com)
  • Based on our novel findings, we are interested on the effects of the PAR2 activation by thrombomodulin-bound thrombin on the alveolar barrier. (usz.ch)
  • VhH anti-TM clone 1 bound recombinant thrombomodulin with a binding affinity (KD) of 1.7±0.4nM and showed binding to native thrombomodulin. (isth.org)
  • The antigen described as BDCA-3 has turned out to be identical to thrombomodulin. (wikipedia.org)
  • Affinity was determined with Surface Plasmon Resonance and binding to native thrombomodulin was confirmed with flow cytometry. (isth.org)