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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The amounts of tissue factor (TF) expressed by brain microvascular endothelial cells (BMECs) from normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were compared after stimulating the cells with different doses of lipopolysaccharide (LPS), thrombin, phorbol myristic acid (PMA), Ca(2+)-ionophore (A23187), or tumor necrosis factor (TNF) and interleukin-1 (IL-1). Treatment of cultured BMECs from WKY and SHR with all of these factors dose-dependently increased their total amount of TF; no substantive differences in the levels of enhanced TF expression were observed between WKY and SHR BMECs. We conclude that stimulated endothelium from rats with hypertension, a major stroke risk factor, is not hyperresponsive with respect to TF expression when compared to normotensive controls.
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PMID:Comparison of stimulated tissue factor expression by brain microvascular endothelial cells from normotensive (WKY) and hypertensive (SHR) rats. 147 6

A highly sensitive automated method, fluorogenic prothrombin time (FPT) method, was developed by a combination of a fluorogenic peptide substrate for thrombin and a centrifugal autoanalyzer (Cobas Bio). Using plasmas from stroke patients, we showed that the second reagent containing fluorogenic peptide substrate should be mixed after the first reagent containing tissue factor and plasma were mixed, that is, two steps method, in order to detect hypercoagulable state. When the first and the second reagent were mixed with plasma at the same time, that is, one step method, FPT was not sensitive to hypercoagulable state. We also showed that patient plasmas should be stored at -80 degrees C and subjected to FPT analysis immediately after thawing, not leaving at 4 degrees C or room temperature. Good correlation was observed on FPT of stroke patients using human tissue factor and bovine tissue factor. Another fluorogenic method was developed by the same principle for the evaluation of factors X and VII concentrations in plasma using deficient plasma of factor X or factor VII. Good correlation was observed on factors X and VII concentrations of stroke patients using human tissue factor and bovine tissue factor.
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PMID:[A basic study on a highly sensitive automated method for hypercoagulable state in plasma, fluorogenic prothrombin time (FPT) method]. 825 61

Tissue factor pathway of coagulation plays a dominant role during normal haemostasis. Tissue factor pathway inhibitor (TFPI), expressed primarily by the microvascular endothelium, appears to be the major physiologic inhibitor of TF-induced coagulation. TF-initiated coagulation also plays an important role in the pathophysiology of many diseases including coronary thrombosis, sepsis, disseminated intravascular coagulation, stroke, cancer, acute respiratory distress syndrome, and ischemia-reperfusion injury. Several animal studies have found a beneficial effect of anti-TF monoclonal antibodies and, recombinant TFPI in some of the above clinical conditions. rTFPI is presently being used in clinical trials in patients with sepsis and in those following microvascular surgery. This article discusses many of the animal studies addressing inhibition of TF-induced coagulation, as well as potential therapeutic uses of rTFPI in humans.
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PMID:Tissue factor pathway inhibitor: potential therapeutic applications. 919 99

Monocyte chemoattractant protein-1 (MCP-1) is a C-C chemokine thought to play a major role in recruiting monocytes to the atherosclerotic plaque. Tissue factor (TF), the initiator of coagulation, is found in the atherosclerotic plaque, macrophages, and human aortic smooth muscle cells (SMC). The exposure of TF during plaque rupture likely induces acute thrombosis, leading to myocardial infarction and stroke. This report demonstrates that MCP-1 induces the accumulation of TF mRNA and protein in SMC and in THP-1 myelomonocytic leukemia cells. MCP-1 also induces TF activity on the surface of human SMC. The induction of TF by MCP-1 in SMC is inhibited by pertussis toxin, suggesting that the SMC MCP-1 receptor is coupled to a Gi-protein. Chelation of intracellular calcium and inhibition of protein kinase C block the induction of TF by MCP-1, suggesting that in SMC it is mediated by activation of phospholipase C. SMC bind MCP-1 with a Kd similar to that previously reported for macrophages. However, mRNA encoding the macrophage MCP-1 receptors, CCR2A and B, is not present in SMC, indicating that they possess a distinct MCP-1 receptor. These data suggest that in addition to being a chemoattractant, MCP-1 may have a procoagulant function and raise the possibility of an autocrine pathway in which MCP-1, secreted by SMC and macrophages, induces TF activity in these same cells.
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PMID:Tissue factor is induced by monocyte chemoattractant protein-1 in human aortic smooth muscle and THP-1 cells. 935 21

Activation of blood coagulation and fibrinolysis has previously been detected in stroke patients. It is unknown, however, what factors contribute to the acceleration of coagulation reactions, especially in cases where no obvious predisposing factors exist. We therefore postulated and tested the hypothesis that in such patients monocytes may trigger the pathway leading to thrombosis by expressing tissue factor (TF). TF antigen was determined in 48 patients and 40 controls by flow cytometry using an indirect immunofluorescent technique. TF antigen expression was significantly increased on monocytes in young stroke patients in both the acute (p < 0.01) and chronic (p < 0.05) phases of the disease. The TF antigen also possessed functional activity, quantitated by a one-stage clotting assay. TF expression on monocytes was not associated with an elevation in C-reactive protein values. In both acute and chronic phases, blood coagulation activation markers, e.g. the thrombin-antithrombin complex and F1 + 2 fragments, were significantly elevated. However, in the acute phase D-dimer levels were similar to those in controls and were only elevated in the chronic phase of the disease (p < 0.05). In conclusion, in cerebral ischemia TF expression on monocytes suggests enhanced activation of blood coagulation and subsequent fibrinolysis.
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PMID:Monocytes express tissue factor in young patients with cerebral ischemia. 968 64

Thrombosis is a key feature of the initiation and progression of atherosclerosis and its clinical sequelae. Acute thrombosis can lead to arterial occlusion and consequently provoke myocardial infarction, unstable angina, stroke and sudden death. Acute thrombosis can also be a complication of arterial bypass surgery, balloon angioplasty, atherectomy, or coronary artery stenting. The thrombotic response is influenced by several factors, among them the thrombogenicity of the vessel wall and of certain blood components as well as their interaction with the lipid pool. Tissue factor (TF) is considered to be the primary cofactor of cellular origin that is involved in activation of the coagulation pathway. The active form of TF has been shown to be present in specimens of human coronary artery in association both with acellular lipid areas and with macrophages and smooth muscle cells, which suggests that TF plays a major role in determining plaque thrombogenicity. We discuss here what is currently known about the role of tissue factor in atherogenesis, and focus attention on pharmacological approaches in this area.
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PMID:Tissue factor in atherosclerosis. 1040 89

There is evidence that inflammatory cytokines such as IL-1beta, TNFalpha, and IL-6 are involved in the pathogenesis of cerebrovascular disorders including stroke. One action of cytokines that contributes to diseases in peripheral tissues is upregulation of the procoagulant receptor tissue factor (TF). In the CNS, astrocytes are the primary cells that express TF; although little is known about how TF is regulated in these cells. Experiments were performed to evaluate the effect of cytokine treatment on TF activity in primary cultures of murine cortical astrocytes and in the human astrocytoma cell line (CCF). IL-1beta treatment induced a 2.5-fold increase in TF activity in the primary astrocytes and a 3-fold induction in the astrocytoma cells. TNFalpha treatment induced a 2.5-fold increase in TF activity in both the primary astrocytes and astrocytoma cells. IL-6 upregulated TF activity 2-fold in primary astrocytes, however, it had no effect on TF activity in the astrocytoma cells. The signaling pathways regulating TF expression in these cells were examined by using staurosporine, a broad spectrum inhibitor of serine-threonine protein kinases, and by examining the effects of intermediates in the sphingomyelin signaling pathway. Staurosporine inhibited IL-1beta-induced TF activity in the primary astrocytes but did not effect IL-1beta- or TNFalpha-induced TF activity in the astrocytoma cells. TF activity in the astrocytoma cells was upregulated 1.5-fold over constitutive levels by a ceramide analogue or the enzyme sphingomyelinase, however the ceramide analogue had no effect on TF activity in the primary astrocytes. These results suggest inflammatory cytokines can upregulate TF activity in astrocytes and the astrocytoma CCF cell line although the two cell types appear to utilize different signaling pathways to mediate TF expression. Further studies will be important to more completely define the signaling regulation of TF in astrocytes since alterations in brain TF levels may play a key role in CNS pathophysiology.
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PMID:Cytokine and intracellular signaling regulation of tissue factor expression in astrocytes. 1073 12

Hemostasis factors may influence the pathophysiology of stroke. The role of brain hemostasis in ischemic hypertensive brain injury is not known. We studied ischemic injury in spontaneously hypertensive rats in relation to cerebrovascular fibrin deposition and activity of different hemostasis factors in brain microcirculation. In spontaneously hypertensive rats subjected to transient middle cerebral artery occlusion versus normotensive Wistar-Kyoto (W-K) rats, infarct and edema volumes were increased by 6.1-fold (P < 0.001) and 5.8-fold (P < 0.001), respectively, the cerebral blood flow (CBF) reduced during middle cerebral artery occlusion (MCAO) by 55% (P < 0.01), motor neurologic score increased by 6.9-fold (P < 0.01), and cerebrovascular fibrin deposition increased by 6.8-fold (P < 0.01). Under basal conditions, brain capillary protein C activation and tissue plasminogen activator activity were reduced in spontaneously hypertensive rats compared with Wistar-Kyoto rats by 11.8-fold (P < 0.001) and 5.1-fold (P < 0.001), respectively, and the plasminogen activator inhibitor-1 antigen and tissue factor activity were increased by 154-fold (P < 0.00001) and 74% (P < 0.01), respectively. We suggest that hypertension reduces antithrombotic mechanisms in brain microcirculation, which may enhance cerebrovascular fibrin deposition and microvascular obstructions during transient focal cerebral ischemia, which results in greater neuronal injury.
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PMID:Brain injury and cerebrovascular fibrin deposition correlate with reduced antithrombotic brain capillary functions in a hypertensive stroke model. 1089 83

Activated monocytes may contribute to the pathogenesis of ischemic stroke. We tested the hypothesis that release products and procoagulant activity of monocytes are increased in acute ischemic stroke. In patients on days 1, 3 and 7 after ischemic stroke and in age- and sex-matched healthy control subjects, we assessed plasma levels of interleukin 8 (IL-8) and neopterin (enzyme linked immunosorbent assay, ELISA) and investigated superoxidanion release (ferricytochrome C reduction), procoagulant activity (one-stage clotting assay) and tissue factor (TF) gene transcription (reverse transcriptase polymerase chain reaction) by monocytes. As compared to control subjects (n=23), IL-8 levels were increased on day 1 after stroke (n=22; p=0.005) and remained elevated on days 3 and 7. Neopterin levels were elevated on days 3 and 7 (p<0.05, respectively) but not on day 1. Neopterin and IL-8 were not correlated with monocyte counts. Superoxid anion production by stimulated and unstimulated monocytes was not different between groups. TF mRNA could neither be detected in monocytes from patients investigated within 12 h after ischemia (n=12) nor in control subjects (n=10) and procoagulant activity of cells was similar in both groups. Our results indicate increased monocyte activation after ischemic stroke although not all activation parameters were elevated. We found no support for the hypothesis that circulating monocytes express TF and possess increased procoagulant activity. Elevated IL-8 may contribute to stroke pathophysiology by activating polymorphonuclear leukocyte (PMNL) activation early after ischemia.
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PMID:Monocyte function and plasma levels of interleukin-8 in acute ischemic stroke. 1170 Nov 51

Cardiopulmonary bypass (CPB) is routinely utilized to provide circulatory support during cardiac surgical procedures. The morbidity of CPB has been significantly reduced since its introduction 50 years ago; however, cerebral injury remains a potentially serious consequence of otherwise successful surgery. The risk of stroke postoperatively is approximately 1-5%. Incidence rates for neurocognitive deficit, however, vary markedly depending on the detection method, although typically it is reported in at least 50% of patients. The aetiology of this cerebral injury remains open to debate, although evidence shows that ischaemia secondary to microembolism may be the principal factor. Emboli originate from bubbles of air, atheroemboli released on aortic manipulation and thromboemboli generated as a result of haemostatic activation. Significant generation of thrombin occurs during CPB resulting in fibrin formation, although the trigger of this activation is not fully understood. Rather than originating from contact activation as previously thought, the primary trigger may be via the activated factor VII/tissue factor pathway of coagulation, with an additional role of contact activation in amplification of coagulation as well as the fibrinolytic response to CPB. Haemostatic activation is inhibited with systemic heparin therapy. The relationship between haemostatic activation and emboli formation during CPB is not known. Interventions to reduce cerebral injury in the context of cardiac surgery depend, in large part, on the minimization of emboli. This review investigates cerebral injury after cardiac surgery and evidence showing that microembolism is the principal causative agent. Fibrin emboli are postulated to be an important source of cerebral embolism. The mechanism of haemostatic activation during CPB is therefore also discussed.
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PMID:Alterations to haemostasis following cardiopulmonary bypass and the relationship of these changes to neurocognitive morbidity. 1173 60


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