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Condition: Thrombosis

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Total 185 results found since Jan 2013.

Accumulation of tissue factor in endothelial cells induces cell apoptosis, mediated through p38 and p53 activation.
In conclusion, accumulation of TF within endothelial cell, or sequestered from the surrounding can induce cellular apoptosis through mechanisms mediated by p38, and involves the stabilisation of p53. PMID: 25903973 [PubMed - as supplied by publisher]
Source: Thrombosis and Haemostasis - April 23, 2015 Category: Hematology Authors: ElKeeb AM, Collier ME, Maraveyas A, Ettelaie C Tags: Thromb Haemost Source Type: research

NMMHCIIA inhibition impedes tissue factor expression and venous thrombosis via Akt/GSK3β-NF-κB signalling pathways in the endothelium.
Abstract Non-muscle myosin heavy chain IIA (NMMHC IIA) has been shown to be involved in thrombus formation and inflammatory microparticle release in endothelial cells. However, the role of NMMHC IIA in regulating the expression of tissue factor (TF) and deep venous thrombosis remains to be elucidated. In the present study, endothelial cells were stimulated with tumour necrosis factor-α (TNF-α) to induce TF expression. Pretreatment with the NMMHC II inhibitor blebbistatin suppressed the mRNA and protein expressions as well as the procoagulant activity of TF in a dose-dependent manner. Blebbistatin enhanced Akt an...
Source: Thrombosis and Haemostasis - April 16, 2015 Category: Hematology Authors: Zhai K, Tang Y, Zhang Y, Li F, Wang Y, Cao Z, Yu J, Kou J, Yu B Tags: Thromb Haemost Source Type: research

Inorganic polyphosphate elicits pro‐inflammatory responses through activation of the mammalian target of rapamycin complexes 1 and 2 in vascular endothelial cells
ConclusionsPolyP, through interaction with RAGE and P2Y1, activates both the mTORC1 and mTORC2 signaling network. Both the pro‐inflammatory and mTOR signaling functions of polyP are linked.
Source: Journal of Thrombosis and Haemostasis - April 13, 2015 Category: Hematology Authors: S. M. Hassanian, P. Dinarvand, S. A. Smith, A. R. Rezaie Tags: Original Article Source Type: research

siRNA Mediated Knockdown of Tissue Factor Expression in Pigs for Xenotransplantation
Abstract Acute vascular rejection (AVR), in particular microvascular thrombosis, is an important barrier to successful pig‐to‐primate xenotransplantation. Here, we report the generation of pigs with decreased tissue factor (TF) levels induced by small interfering (si)RNA‐mediated gene silencing. Porcine fibroblasts were transfected with TF‐targeting small hairpin (sh)RNA and used for somatic cell nuclear transfer. Offspring were analyzed for siRNA, TF mRNA and TF protein level. Functionality of TF downregulation was investigated by a whole blood clotting test and a flow chamber assay. TF siRNA was expressed in all ...
Source: American Journal of Transplantation - March 23, 2015 Category: Transplant Surgery Authors: H. E. Ahrens, B. Petersen, D. Herrmann, A. Lucas‐Hahn, P. Hassel, M. Ziegler, W. A. Kues, U. Baulain, W. Baars, R. Schwinzer, J. Denner, D. Rataj, S. Werwitzke, A. Tiede, A. K. Bongoni, P. S. Garimella, A. Despont, R. Rieben, H. Niemann Tags: Brief Communication Source Type: research

Titrating haemophilia B phenotypes using siRNA strategy: evidence that antithrombotic activity is separated from bleeding liability.
Abstract Haemophilia A and B are characterised by a life-long bleeding predisposition, and several lines of evidence suggest that risks of atherothrombotic events may also be reduced. Establishing a direct correlation between coagulation factor levels, thrombotic risks and bleeding propensity has long been hampered by an inability to selectively and specifically inhibit coagulation factor levels. Here, the exquisite selectivity of gene silencing combined with a gene knockout (KO) approach was used to define the relative contribution of factor IX (fIX) to thrombosis and primary haemostasis in the rat. Using a lipid...
Source: Thrombosis and Haemostasis - March 19, 2015 Category: Hematology Authors: Metzger JM, Tadin-Strapps M, Thankappan A, Strapps WR, Di Poetro M, Leander K, Zhang Z, Shin MK, Levorse J, Desai K, Xu Y, Lai K, Wu W, Chen Z, Cai TQ, Jochnowitz N, Bentley R, Hoos L, Zhou Y, Sepp-Lorenzino L, Seiffert D, Andre P Tags: Thromb Haemost Source Type: research

Inorganic polyphosphate elicits proinflammatory responses through activation of mTOR complexes 1 and 2 in vascular endothelial cells
ConclusionsPolyP, through interaction with RAGE and P2Y1, activates both mTORC1 and mTORC2 signaling network. Both proinflammatory and mTOR signaling functions of polyP are linked.This article is protected by copyright. All rights reserved.
Source: Journal of Thrombosis and Haemostasis - March 16, 2015 Category: Hematology Authors: Seyed Mahdi Hassanian, Peyman Dinarvand, Stephanie A. Smith, Alireza R. Rezaie Tags: Original Article ‐ Vascular Biology Source Type: research

Inorganic polyphosphate elicits proinflammatory responses through activation of mTOR complexes 1 and 2 in vascular endothelial cells.
CONCLUSIONS: PolyP, through interaction with RAGE and P2Y1 , activates both mTORC1 and mTORC2 signaling network. Both proinflammatory and mTOR signaling functions of polyP are linked. This article is protected by copyright. All rights reserved. PMID: 25776944 [PubMed - as supplied by publisher]
Source: Thrombosis and Haemostasis - March 16, 2015 Category: Hematology Authors: Hassanian SM, Dinarvand P, Smith SA, Rezaie AR Tags: J Thromb Haemost Source Type: research

Protein disulphide-isomerase A2 regulated intracellular tissue factor mobilisation in migrating human vascular smooth muscle cells.
In conclusion, we demonstrate that TF is chaperoned by PDIA2 to the HVSMC membrane and to the cell migratory front. Absence of PDIA2 impairs TF intracellular trafficking to its membrane docking favoring its uncontrolled release in microparticles. TF-regulated HVSMC migration and microvessel formation is under the control of the ER-protein PDIA2. PMID: 25631539 [PubMed - as supplied by publisher]
Source: Thrombosis and Haemostasis - January 29, 2015 Category: Hematology Authors: Peña E, Arderiu G, Badimon L Tags: Thromb Haemost Source Type: research

The cell-membrane prothrombinase, fibrinogen-like protein 2, promotes angiogenesis and tumor development
The aim of the study was to further investigate the role of fibrinogen-like protein 2 (FGL-2), a transmembrane prothrombinase that directly cleaves prothrombin to thrombin, in angiogenesis and tumor development and the mechanism(s) underlying these processes. To study angiogenesis HUVEC clones with decreased fgl-2 mRNA were generated by specific siRNA. To study tumorigenesis SCID mice were implanted with intact (wild type) and fgl-2-silenced PC-3 clones. IFN-γ treated HUVEC expressing increased fgl-2 mRNA exhibited significant capillary sprouting that was not inhibited by hirudin, whereas fgl-2 silencing completely inhibi...
Source: Thrombosis Research - December 4, 2014 Category: Hematology Authors: Esther Rabizadeh, Izhack Cherny, Doron Lederfein, Shany Sherman, Natalia Binkovsky, Yevgenia Rosenblat, Aida Inbal Tags: Regular Article Source Type: research

Gas6-induced tissue factor expression in endothelial cells is mediated through caveolin-1-enriched microdomains.
CONCLUSION: Gas6 induced Axl and c-Src localization into lipid raft/caveolin-1-enriched fractions. Gas6 increased the phosphorylation of Akt, ERK1/2, and c-Src but not p38. Using siRNA, we demonstrated that Axl is required for Akt, ERK1/2, and c-Src activation after Gas6 stimulation. siRNA for caveolin-1 blocked Gas6-induced phosphorylation of Akt, ERK1/2, and c-Src. c-Src downregulation inhibited Gas6-induced Akt but not ERK1/2 phosphorylation. Finally, Gas6 increased tissue factor mRNA and protein expression in endothelial cells. Tissue factor expression was blocked by siRNA for Axl, caveolin-1, or Akt as well as c-Src i...
Source: Thrombosis and Haemostasis - November 15, 2014 Category: Hematology Authors: Laurance S, Aghourian MN, Jiva Lila Z, Lemarié CA, Blostein MD Tags: J Thromb Haemost Source Type: research

Protein S exacerbates alcoholic hepatitis by stimulating liver natural killer T cells
ConclusionsThe results of this study suggest that PS exacerbates acute alcoholic hepatitis by inhibiting apoptosis of activated NKT cells.This article is protected by copyright. All rights reserved.
Source: Journal of Thrombosis and Haemostasis - November 1, 2014 Category: Hematology Authors: Ayshwarya‐Lakshmi Chelakkot‐Govindalayathil, Rumi Mifuji‐Moroka, Corina N. D’ Alessandro‐Gabazza, Masaaki Toda, Yoshikazu Matsuda, Paloma Gil‐Bernabe, Ziaurahman Roeen, Taro Yasuma, Yutaka Yano, Esteban C Gabazza, Motoh Iwasa, Yoshiyuki Takei Tags: Original Article ‐ Vascular Biology Source Type: research

Glioblastoma microvesicles promote endothelial cell proliferation through Akt/beta-catenin pathway.
In conclusion, glioblastoma mainly affects microvesicles within CSF without showing significant impact on microvesicles in circulating blood. Microvesicles from the CSF of glioblastoma patients may initiate endothelial cell growth and thus promote cell invasion. This effect may be directly exerted by activated Akt/beta-catenin pathway. PMID: 25197356 [PubMed - in process]
Source: International Journal of Clinical and Experimental Pathology - September 15, 2014 Category: Pathology Authors: Liu S, Sun J, Lan Q Tags: Int J Clin Exp Pathol Source Type: research

IKKβ regulates endothelial thrombomodulin in a Klf2‐dependent manner
ConclusionsIKK inhibition increased TM expression and function, and attenuated TNF‐mediated TM down‐regulation. In contrast, inhibition of down‐stream canonical NF‐B protein family members p50 and p65 (RelA) failed to up‐regulate TM expression and did not affect IKK inhibition–mediated TM over‐expression. However, knockdown of cRel and RelB, family members of the canonical and non‐canonical NF‐κB pathway, respectively, resulted in TM over‐expression. IKK inhibition caused over‐expression, increased promoter activity and enhanced binding of Krüppel‐like factor 2 (Klf2) to the TM prom...
Source: Journal of Thrombosis and Haemostasis - July 14, 2014 Category: Hematology Authors: R. Pathak, L. Shao, S. M. Chafekar, W. Feng, U. Ponnappan, L.M. Fink, D. Zhou, M. Hauer‐Jensen Tags: Original Article ‐ Coagulation Source Type: research

Chloride intracellular channel 1 participates in migration and invasion of hepatocellular carcinoma by targeting maspin
ConclusionsCLIC1 protein expression is significantly correlated with vascular invasion, and the present study suggests a previously unknown mechanism of CLIC1‐mediated control of HCC invasiveness by targeting maspin.
Source: Journal of Gastroenterology and Hepatology - July 2, 2014 Category: Gastroenterology Authors: Xuyong Wei, Jie Li, Haiyang Xie, Hangxiang Wang, Jianguo Wang, Xuanyu Zhang, Runzhou Zhuang, Di Lu, Qi Ling, Lin Zhou, Xiao Xu, Shusen Zheng Tags: Experimental Hepatology Source Type: research

NF‐κB is activated from endosomal compartments in antiphospholipid antibodies‐treated human monocytes
ConclusionWe show that TLR2 and its co‐receptors, TLR1 and TLR6, contribute to the pathogenicity of aPLA, that aPLA are internalized via clathrin‐ and CD14‐dependent endocytosis and that endocytosis is required for NF‐κB activation. Our results contribute to a better understanding of the APS and provide a possible therapeutic approach.
Source: Journal of Thrombosis and Haemostasis - May 22, 2014 Category: Hematology Authors: K. J. Brandt, C. Fickentscher, F. Boehlen, E. K. O. Kruithof, P. Moerloose Tags: In Focus Source Type: research