Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transmembrane receptor tissue factor is a prominent protein expressed at macrophages and smooth muscle cells within human atherosclerotic lesions. While many coagulation proteins are detectable in atherosclerosis, a locally active thrombin and fibrin generating molecular machinery may be instrumental in manipulating cellular functions involved in atherogenesis. These include inflammation, angiogenesis and cell proliferation. Indeed, many experimental studies in mice show a correlation between hypercoagulability and increased atherosclerosis. In mice, the amount of atherosclerosis and/or the plaque phenotype, appear to be modifiable by specific anticoagulant interventions. While attempts to vary tissue factor level in the vasculature does not directly reduce plaque burden, the overexpression of tissue factor pathway inhibitor attenuates thrombogenicity and neo intima formation in mice. Moreover, inhibition of factor Xa or thrombin with novel selective agents, including rivaroxaban and dabigatran, inhibits inflammation associated with atherosclerosis in apoE(-/-) mice. The potential to modify a complex chronic disease like atherosclerosis with novel selective anticoagulants merits further clinical study.
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PMID:Tissue factor-driven thrombin generation and inflammation in atherosclerosis. 2239 11

Dyslipidemia is a risk factor for clinically significant thrombotic events. In this condition, scavenger receptor CD36 potentiates platelet reactivity through recognition of circulating oxidized lipids. CD36 promotes thrombosis by activating redox-sensitive signaling molecules, such as the MAPK extracellular signal-regulated kinase 5 (ERK5). However, the events downstream of platelet ERK5 are not clear. In this study, we report that oxidized low-density lipoprotein (oxLDL) promotes exposure of procoagulant phosphatidylserine (PSer) on platelet surfaces. Studies using pharmacologic inhibitors indicate that oxLDL-CD36 interaction-induced PSer exposure requires apoptotic caspases in addition to the downstream CD36-signaling molecules Src kinases, hydrogen peroxide, and ERK5. Caspases promote PSer exposure and, subsequently, recruitment of the prothrombinase complex, resulting in the generation of fibrin from the activation of thrombin. Caspase activity was observed when platelets were stimulated with oxLDL. This was prevented by inhibiting CD36 and ERK5. Furthermore, oxLDL potentiates convulxin/glycoprotein VI-mediated fibrin formation by platelets, which was prevented when CD36, ERK5, and caspases were inhibited. Using 2 in vivo arterial thrombosis models in apoE-null hyperlipidemic mice demonstrated enhanced arterial fibrin accumulation upon vessel injury. Importantly, absence of ERK5 in platelets or mice lacking CD36 displayed decreased fibrin accumulation in high-fat diet-fed conditions comparable to that seen in chow diet-fed animals. These findings suggest that platelet signaling through CD36 and ERK5 induces a procoagulant phenotype in the hyperlipidemic environment by enhancing caspase-mediated PSer exposure.
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PMID:Platelet CD36 signaling through ERK5 promotes caspase-dependent procoagulant activity and fibrin deposition in vivo. 3038 1

Endobronchial biopsy (EBB)-induced bleeding is fairly common; however, it can be potentially life-threatening due to difficult hemostasis following EBB. The aim of this study was to develop a predictive model of difficult hemostasis post-EBB. A total of 620 consecutive patients with primary lung cancer who had undergone EBB between 2014 and 2018 in a large tertiary hospital were enrolled in this retrospective single-center cohort study. Patients were classified into the difficult hemostasis group and the nondifficult hemostasis group according to hemostatic measures used following EBB. The LASSO regression method was used to select predictors and multivariate logistic regression was applied to develop the predictive model. The area under the curve (AUC) of the model was calculated. Bootstrapping method was applied for internal validation. Calibration curve analysis and decision curve analysis (DCA) were also performed. A nomogram was constructed to display the model. The incidence of difficult hemostasis post-EBB was 11.9% (74/620). Eight variables were selected by the LASSO regression analysis and seven (histological type of cancer, lesion location, neutrophil percentage, activated partial thromboplastin time, low density lipoprotein cholesterol, apolipoprotein-E, and pulmonary infection) of them were finally included in the predictive model. The AUC of the model was 0.822 (95% CI, 0.777-0.868), and it was 0.808 (95% CI, 0.761-0.856) in the internal validation. The predictive model was well calibrated and DCA indicated its potential clinical usefulness, which suggests that the model has great potential to predict lung cancer patients with a more difficult post-EBB hemostasis.
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PMID:Development of a Predictive Model of Difficult Hemostasis following Endobronchial Biopsy in Lung Cancer Patients. 3093 21


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