Abstract:
:Understanding the intracellular events triggered by antiphospholipid (aPL) antibodies in platelets and endothelial cells (ECs) is important in designing new modalities of targeted therapies for the treatment of thrombosis in Antiphospholipid Syndrome (APS). A recent study showed a significant increase in the expression of GPIIb/IIIa on platelets treated with aPL antibodies and a thrombin receptor peptide agonist (TRAP), and these effects were abrogated by hydroxychloroquine (HQ). Hydroxychloroquine has also been shown to reduce in vivo aPL-induced thrombus formation. Furthermore, aPL-enhanced thrombosis in vivo can be abrogated by infusions of a GPIIb/IIIa antagonist (1B5) monoclonal antibody, and aPL-mediated thrombophilia is not observed in GPIIb/IIIa-deficient mice. Treatment of platelets with aPL antibodies has resulted in a significant increase in p38 mitogen-activated protein kinase (p38MAPK) phosphorylation and aPL-induced platelet aggregation and thromboxane B2 (TXB2) production was abrogated by SB203580 (a p38MAPK inhibitor). aPL antibodies induce increased expression, function and transcription of tissue factor (TF) on EC. Activation of ECs and thrombogenicity of aPL in vivo can be reversed by treatment of the animals with statins. Upregulation of TF on ECs can also be abrogated by treatment of the cells with fluvastatin. There is also indication of activation of nuclear factor kappa B (NFkappaB), increase in phosphorylation of p38MAPK in ECs by aPL antibodies that can be reversed by specific inhibitors MG132 and SB203580, respectively. The data open the possibility to new treatment modalities that may include the use of hydroxychloroquine, statins, specific antagonists of GPIIb/IIIa (such as abciximab or equivalent) and specific p38MAPK inhibitors, after the completion of well-designed clinical studies.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Pierangeli SS,Vega-Ostertag M,Harris ENdoi
10.1016/j.thromres.2004.06.031subject
Has Abstractpub_date
2004-01-01 00:00:00pages
467-76issue
5-6eissn
0049-3848issn
1879-2472pii
S0049-3848(04)00340-8journal_volume
114pub_type
杂志文章,评审abstract::The need for anticoagulation in dialysis patients is common and the incidence of venous thromboembolism (VTE) and atrial fibrillation in this population is high. While direct data are lacking on the management of anticoagulation in dialysis patients, careful weighing of risks and benefits on the basis of evidence from...
journal_title:Thrombosis research
pub_type: 杂志文章,实务指引
doi:10.1016/j.thromres.2005.03.031
更新日期:2006-01-01 00:00:00
abstract::One of the major pathogens of periodontitis, Porphyromonas gingivalis (P. gingivalis), has the ability to aggregate human platelets. To investigate the interaction between P. gingivalis and human platelets in platelet rich plasma (PRP), platelet aggregation was measured by an aggregometer based on laser light scatteri...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2008.03.011
更新日期:2008-01-01 00:00:00
abstract::The release of arachidonic acid, and its subsequent conversion to thromboxane A2, is an important component of platelet activation. The precise mechanism of arachidonic acid release is unknown although cytosolic phospholipase A2 (cPLA2) has been implicated. In the present study the effects of three agonists, the serin...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(98)00097-8
更新日期:1998-10-01 00:00:00
abstract:INTRODUCTION:Although accumulating evidence within the past 5 years strongly supports the importance of platelet P2X(1) receptors in hemostasis and thrombosis, P2X(1) receptors of platelet and/or its progenitor cell, megakaryocyte, have not been fully characterized. The aim of this study was to electrophysiologically a...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2006.03.007
更新日期:2007-01-01 00:00:00
abstract:INTRODUCTION:Cytomegalovirus (CMV)-associated thrombosis has been reported sporadically in the medical literature until now. However, thrombosis incidence and its risk factors have never been studied in a cohort of patients with acute CMV infection. MATERIALS AND METHODS:A retrospective case-control study. Medical cha...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2010.09.006
更新日期:2010-12-01 00:00:00
abstract::The antithrombotic effect of aspirin (ASA) and dipyridamole (DIP) was evaluated in rabbits in which platelet thromboxane A2 (TXA2) and arterial prostacyclin (PGI2) were measured. An intracarotid cannula thrombosis model previously shown to be sensitive to antiplatelet agents was used. Prostaglandins were determined by...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(83)90224-4
更新日期:1983-05-15 00:00:00
abstract:BACKGROUND:Thrombin is the most potent platelet activator, and achieves rapid platelet activation even in the presence of antiplatelet therapy. Since activated platelets respond stronger to additional stimuli, the extent of endogenous thrombin generation may in part be responsible for the reported response variability ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2013.04.008
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND:Plasma coagulation Factor XII (FXII) plays a crucial role in contact activation, ultimately regulating both the kinin-kallikrein system and the intrinsic pathway of coagulation. A growing body of evidence suggests that inhibition of FXII can prevent thrombosis. Given FXII does not appear to modulate hemostas...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2020.08.040
更新日期:2020-12-01 00:00:00
abstract::Epidemiologic data have indicated that the intake of polyphenols is inversely associated with mortality from cardiovascular disease. Mitogen-activated protein kinases (MAPKs) are ubiquitous signaling proteins that have been associated with gene regulation. This study determined whether polyphenols (catechin and querce...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2007.02.001
更新日期:2007-01-01 00:00:00
abstract:INTRODUCTION:Aspirin is a common antiplatelet drug used in the prevention of ischemic stroke due to its inhibitory effect on platelet cyclooxygenase-1 (Cox-1). Patients can be categorized as either aspirin 'responders' or 'non-responders' depending on whether they are protected against a secondary stroke event or not. ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2003.12.005
更新日期:2003-01-01 00:00:00
abstract::Recombinant factor IX (rFIX) is increasingly used to treat patients with hemophilia B. CHO (Chinese Hamster Ovary) cells are commonly used for the production of rFIX but they have a limited capacity for introducing post-translational modifications (PTM) leading to incomplete γ-carboxylation, low phosphorylation and su...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2012.08.313
更新日期:2012-11-01 00:00:00
abstract:INTRODUCTION:Extracellular histones are reported to increase thrombin generation in the plasma and induce endothelial cell death in vitro. These effects of histones were suggested to involve histone-induced inhibition of TM-dependent activated protein C (APC) generation. Therefore, we hypothesized that TM alfa, a recom...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2017.10.019
更新日期:2017-12-01 00:00:00
abstract::Annexin V is a human phospholipid binding protein (M(r) 36,000) that binds with high affinity to activated platelets in vitro. We studied the biodistribution and thrombus binding of annexin V in rabbit and swine models of fully occlusive arterial thrombi formed 1-2 h prior to injection of annexin V. Iodinated annexin ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(94)90224-0
更新日期:1994-09-01 00:00:00
abstract:BACKGROUND:Right heart dysfunction is a crucial factor in risk stratification of normotensive patients with pulmonary embolism. Apart from biomarkers, determinants of right heart dysfunction in this group of patients are not yet well established. AIM AND METHOD:In order to identify such determinants, we analysed data ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2010.06.009
更新日期:2010-09-01 00:00:00
abstract:INTRODUCTION:Many antithrombotic drugs may have a deleterious effect on normal haemostasis leading to bleeding complications. The aim of this study was to determine if sub-therapeutic (low) doses of antithrombotic agents, when administered in combination, have enhanced efficacy without augmentation of bleeding time. M...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2005.11.015
更新日期:2006-01-01 00:00:00
abstract::Fractalkine/CX3CR1 pathway is considered a major modulator of atherosclerosis. In the present study, expression of CX3CR1 on PBMCs/monocytes of healthy individuals and coronary artery diseased patients was initially assessed by flow cytometry. Effects of pre-inflammatory cytokines interferon (INF)-gamma and tumor necr...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2007.04.005
更新日期:2007-01-01 00:00:00
abstract::Approximately one-fifth of all cases of venous thromboembolism (VTE) are related to cancer. VTE complications may have a substantial impact on prognosis, quality of life and care in patients with cancer. Patients with cancer-related VTE are at increased risk of developing recurrent VTE compared to patients without can...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/S0049-3848(20)30409-6
更新日期:2020-07-01 00:00:00
abstract::Current guidelines recommend performing laboratory tests aimed at monitoring unfractionated heparin (UFH) treatments within a delay not exceeding 1 to 2 h(s) after sampling when blood is collected into citrated tubes. As such a short delay could be an issue, we evaluated the potential impact of longer delays. For that...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2019.10.019
更新日期:2020-02-01 00:00:00
abstract:INTRODUCTION:Prediction of venous thromboembolism (VTE) occurrence in cancer patients using individual risk factors may contribute to preventing the burden of disease associated with VTE. Congestive heart failure in patients with cancer may increase the risk of VTE and worsen the prognosis. AIM:We sought to investigat...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/S0049-3848(16)30134-7
更新日期:2016-04-01 00:00:00
abstract:INTRODUCTION:Hydrogen sulfide (H2S) known as a gasotransmitter is increasingly recognized for its anti-adhesive, anti-inflammatory and vasoactive properties. Due to these properties, we analysed anti-thrombotic effects of H2S and the participation of the nitric oxide synthase (NOS)-pathway. MATERIALS AND METHODS:In in...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2013.07.010
更新日期:2013-08-01 00:00:00
abstract::Tissue factor pathway inhibitor is the major potent physiologic inhibitor of tissue factor-induced coagulation. Several potential binding sites for transcription factors have been described in the 750 bp of the 5' flanking region of the human tissue factor pathway inhibitor gene reported earlier. To identify elements ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(99)00040-7
更新日期:1999-09-01 00:00:00
abstract:INTRODUCTION:Even though thrombocytopenia following transcatheter aortic valve implantation (TAVI) has been described, further investigation of this phenomenon is needed. AIMS:To determine which factors may explain the fall in platelet count that occurs after implantation of a TAVI device, including markers of platele...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2017.05.020
更新日期:2017-08-01 00:00:00
abstract:INTRODUCTION:To determine whether the HIT IgG class platelet factor 4 (PF4) enzyme immunoabsorbant assay (EIA) influenced the duration of parenteral direct thrombin inhibitor (pDTI) therapy or bleeding risk in patients started on pDTI for a presumed diagnosis of HIT. MATERIALS/METHODS:187 patients started on pDTI for ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.04.030
更新日期:2014-07-01 00:00:00
abstract::Ajoene, the major antiplatelet compound derived from garlic, synergistically potentiates the antiaggregatory action of prostacyclin, forskolin, indomethacin and dypiridamole. For collagen-induced platelet aggregation in human PRP, the ID50 for ajoene is 95 +/- 5 microM. However, in the presence of the antiaggregatory ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(86)90259-8
更新日期:1986-05-01 00:00:00
abstract:INTRODUCTION:We examined a 6-month-old girl with inherited fibrinogen abnormality and no history of bleeding or thrombosis. Routine coagulation screening tests showed a markedly low level of plasma fibrinogen determined by functional measurement and also a low level by antigenic measurement (functional/antigenic ratio=...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.06.002
更新日期:2014-08-01 00:00:00
abstract:BACKGROUND:Factor XIII (FXIII), a plasma pro-transglutaminase, consists of two A subunits and two B subunits (FXIIIA2B2). Following activation by thrombin, it cross-links fibrin chains at the final step of coagulation. We previously reported that FXIII subunit A (FXIIIA) serves as a protein disulfide isomerase (PDI), a...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2012.12.003
更新日期:2013-04-01 00:00:00
abstract::Blood was obtained from four patients envenomated by the Australian common brown snake, Pseudonaja textilis textilis. This elapid snake has one of the most toxic venoms in the world, containing extremely potent neurotoxic and coagulant components. The latter is a potent complete prothrombinase, converting prothrombin ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(90)90399-w
更新日期:1990-09-01 00:00:00
abstract::Murine monoclonal antibodies (mAb) were raised to a purified product of bovine PF-4, a 9,500 dalton protein with heparin neutralization activity comparable to that of human PF-4. Using a non-radioactive slide immunoenzymatic assay, four major classes of mAb could be identified when comparisons were made between purifi...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(86)90384-1
更新日期:1986-03-15 00:00:00
abstract:INTRODUCTION:The low-molecular-weight heparins have been demonstrated to have antiangiogenic effects in various assays. We aimed to demonstrate and compare the antiangiogenic effects of four types of commercially available low-molecular weight heparins in the chick embryo chorioallantoic membrane model. MATERIALS AND ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2011.05.005
更新日期:2011-10-01 00:00:00
abstract::Cooperative effects of PAF-acether and arachidonic acid in blood platelet activation were studied in human platelet-rich plasma. Using a combination of low concentrations of PAF-acether and subthreshold amounts of exogenous arachidonic acid an enhancement of aggregation and an increased formation of malondialdehyde ar...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(84)90080-x
更新日期:1984-02-15 00:00:00