Abstract：
:Platelet activation plays a pivotal role in physiological hemostasis and pathological thrombosis causing heart attack and stroke. Previous studies conclude that simultaneous activation of Gi and G12/13 signaling pathways is sufficient to cause platelet aggregation. However, using Gq knockout mice and Gq-specific inhibitors, we here demonstrated that platelet aggregation downstream of coactivation of Gi and G12/13 depends on agonist concentrations; coactivation of Gi and G12/13 pathways only induces platelet aggregation under higher agonist concentrations. We confirmed Gi and G12/13 pathway activation by showing cAMP (cyclic adenosine monophosphate) decrease and RhoA activation in platelets stimulated at both low and high agonist concentrations. Interestingly, we found that though Akt and PAK (p21-activated kinase) translocate to the platelet membrane upon both low and high agonist stimulation, membrane-translocated Akt and PAK only phosphorylate at high agonist concentrations, correlating well with platelet aggregation downstream of concomitant Gi and G12/13 pathway activation. PAK inhibitor abolishes Akt phosphorylation, inhibits platelet aggregation in vitro and arterial thrombus formation in vivo. We propose that the PAK-PI3K/Akt pathway mediates platelet aggregation downstream of Gi and G12/13, and PAK may represent a potential antiplatelet and antithrombotic target.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Zhang J,Zhang Y,Zheng S,Liu Y,Chang L,Pan G,Hu L,Zhang S,Liu J,Kim S,Dong J,Ding Zdoi
10.1055/s-0040-1714745subject
Has Abstractpub_date
2020-11-01 00:00:00pages
1536-1547issue
11eissn
0340-6245issn
2567-689Xjournal_volume
120pub_type
杂志文章abstract：:Malondialdehyde (MDA) is a stable produce of arachidonic acid metabolism, catalyzed by the enzyme cyclo-oxygenase. The experimental conditions for measuring the kinetics of MDA formation in rat citrated platelet-rich plasma were defined. Platelets were stimulated with either arachidonic acid, the substrate of MDA, or ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1980-10-31 00:00:00
abstract：:The endocannabinoid anandamide (AEA) has many neurovascular activities. However, it is not yet clear how AEA can be metabolized at the neurovascular interface, and how it can move through the vascular and the cerebral compartments. The results reported in this article show that isolated bovine brain microvessels, an e...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2006-01-01 00:00:00
abstract：:Tissue factor (TF) is the blood coagulation initiator, whose cofactor function is required for physiological factor VIIa (FVIIa)-mediated activation of factor X (FX) to FXa. A previous study reported TF on herpes simplex virus type 1 (HSV1), but this explained only part of FVIIa-dependent FXa generation observed on th...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH04-04-0242
更新日期：2004-11-01 00:00:00
abstract：:We previously reported that antithrombin (AT) reduced ischemia/reperfusion (I/R)-induced liver injury in rats by increasing endothelial production of prostacyclin (PGI2). However, the mechanism(s) underlying this phenomenon remains to be fully elucidated. We also demonstrated that activation of capsaicin-sensitive sen...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH04-02-0106
更新日期：2005-01-01 00:00:00
abstract：:Wound healing is a complicated biological process that consist of partially overlapping inflammatory, proliferation and tissue remodelling phases. A successful wound healing depends on a proper activation and subsequent termination of the inflammatory phase. The failure to terminate the inflammation halts the completi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH15-08-0653
更新日期：2016-05-02 00:00:00
abstract：:Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with chemokine-like functions. MIF is a critical mediator of the host immune and inflammatory response. Dysregulated MIF expression has been demonstrated to contribute to various acute and chronic inflammatory conditions as well as cancer developme...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH12-11-0831
更新日期：2013-03-01 00:00:00
abstract：:Paired blood samples were obtained from mothers (venous) and babies (cord venous blood) at the time of delivery by caesarean section under epidural anaesthetic. Fetal platelets failed to aggregate in response to adrenaline in vitro although adrenaline could potentiate the threshold response to adenosine diphosphate (1...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1985-02-18 00:00:00
abstract：:Thrombin regulation in newborns remains incompletely understood. We studied tissue factor-initiated thrombin formation in cord plasma in vitro, and the effects of Factor V(Leiden) (FVL) heterozygosity on thrombin regulation both in vitro and in vivo in newborns. Pregnant women with known thrombophilia (n=27) were enro...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH05-05-0375
更新日期：2006-03-01 00:00:00
abstract：:Autoantibodies to the zwitterionic phospholipid (PL), phosphatidylethanolamine (PE) have been described in patients with thrombotic diseases. Recently, we reported that many antiphosphatidylethanolamine antibodies (aPE) are not specific for PE per se, but are directed to plasma proteins which can bind PE, for example,...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1996-09-01 00:00:00
abstract：:The interaction of bovine platelets with bovine glomerular basement membrane has been studied by aggregometry, transmission and scanning electron microscopy and measurement of [3H] serotonin release. In the absence of added calcium platelets adhere to basement membrane but fail to undergo the release reaction or aggre...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1979-12-21 00:00:00
abstract：:Thromboembolic complications have been attributed to the use of radiographic contrast media (CM) during interventional procedures for arterial revascularization. However, due to the low frequency of adverse events, comparisons between different CM have been difficult to perform, although it has been suggested that ion...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-03-01 00:00:00
abstract：:High heparin cofactor II (HCII) activity has recently been described to protect from coronary instent restenosis, presumably by inactivating thrombin in injured arteries. In this study, we investigated the association of HCII activity and restenosis after femoropopliteal stenting. We studied 63 consecutive patients wi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH04-05-0311
更新日期：2004-11-01 00:00:00
abstract：:Patients with both chronic kidney disease (CKD) and diabetes mellitus (DM) are at increased risk for thrombotic events compared to those with one abnormality alone. Whether this can be attributed to changes in platelet reactivity among those with both CKD and DM is unknown. We prospectively studied 438 clopidogrel-naï...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH13-01-0004
更新日期：2013-07-01 00:00:00
abstract：:The increased risk for deep vein thrombosis (DVT) after orthopaedic surgery has been well documented as well as hypercoagulable state during both total hip arthroplasty (THA) and total knee replacement (TKR). To investigate the influence of the surgical procedure [posterolateral (PL) or lateral (L) approach for THA, u...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1999-06-01 00:00:00
abstract：:A procedure for using citrated fresh plasmas for International Sensitivity Index (ISI) calibration of two types of whole blood point-of-care test (POCT) prothrombin time (PT) monitor systems has been assessed in a multicentre study. The CoaguChek Mini and TAS PT-NC systems gave higher ISI with whole blood samples than...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：
更新日期：2002-05-01 00:00:00
abstract：:Vascular endothelial cells perform many differentiated functions in processes such as angiogenesis, hemostasis, and inflammation. The number of recognized differentiated functions has increased rapidly in recent years, but there may be many more still unrecognized. The purpose of this study is to estimate the fraction...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1993-05-03 00:00:00
abstract：:Mature circulating endothelial cells (CECs) are novel cellular markers of endothelial damage/dysfunction. The two main techniques of CEC enumeration are flow cytometry (FC) and immunomagnetic bead (IB) isolation. Both quantify CECs accurately, but a direct comparison of both methods has not been reported. We sought to...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH06-04-0185
更新日期：2006-07-01 00:00:00
abstract：:In the AMPLIFY clinical trial, apixaban was non-inferior to warfarin plus subcutaneous enoxaparin bridge therapy in the treatment of acute venous thromboembolism (VTE) and was associated with significantly less bleeding. This study evaluated their comparative effectiveness and safety in routine clinical practice. A ma...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章
doi：10.1055/s-0038-1673689
更新日期：2018-11-01 00:00:00
abstract：:Human platelets have unique and reproducible mRNA profiles, with evidence for distinct profiles in haematopoietic stem cell disorders associated with thrombocytosis. Platelet transcript profiling is traditionally studied by microarray analysis, quantitative reverse transcription-PCR or serial analysis of gene expressi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2008-11-01 00:00:00
abstract：:Clinical observations have shown that heparin has antiinflammatory activities. The effect of heparin on neutrophil chemotaxis was evaluated in vitro in the Boyden Chamber. This method enabled differentiation between the direct effects of heparin on neutrophil migration and locomotion, and its effects on chemotactic fa...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1984-10-31 00:00:00
abstract：:A method is described for increasing the sensitivity of the thiobarbiturate assay for malondialdehyde by concentrating the coloured reaction product. The basal level of malondialdehyde-like material in plasma was found to be about 0.03 micrometer. Platelets synthesized malondialdehyde when stimulated by collagen or th...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1977-12-15 00:00:00
abstract：:The prophylactic treatment of haemophilia B and the management of haemophilia A or B with inhibitors demand frequent administrations of coagulation factors due to the suboptimal half-lives of the products commercially available and currently in use, e.g. recombinant factor IX (rFIX) and recombinant factor VIIa (rFVIIa...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH13-03-0213
更新日期：2013-11-01 00:00:00
abstract：:Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells. We have studied the production of VEGF by human macrophages in response to lipopolysaccharide (LPS). Macrophages stimulated with LPS expressed VEGF mRNA and protein in concentration- and time-dependent manners. The LPS-induced expression of ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-01-01 00:00:00
abstract：:To investigate the inhibitory mechanism of tissue factor pathway inhibitor (TFPI), an attempt was made to examine the inhibitory activity of TFPI toward the factor VIIa-truncated tissue factor (TF1-219) complex, which lacks its transmembrane and cytoplasmic domains. Factor VIIa-TF1-219 activity was significantly inhib...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-03-01 00:00:00
abstract：:A fibrinolysis inhibitor was purified in serum from post-traumatic patients by the use of flat bed electrofocusing of serum desalted by gel chromatography followed by affinity chromatography on a column of matrix-linked plasminogen. Disc gel electrophoresis yielded one protein band. The inhibitor protein was also foun...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1978-02-28 00:00:00
abstract：:The effect of the ADP receptor antagonists ATP and adenosine 5'-(beta, gamma-methylene)triphosphate (AMP-PCP), and the ADP-utilizing enzyme systems creatine phosphokinase/creatine phosphate (CPK/CP) and pyruvate kinase/phosphoenol pyruvate (PK/PEP) on platelet deposition onto type I collagen was examined. An in vitro ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1992-04-02 00:00:00
abstract：:Human platelets were separated into subpopulations using continuous flow electrophoresis, which uses electrophoretic mobility as the separative parameter. The platelets with the greatest electrophoretic mobility showed higher amounts of total sialic acid than the less electrophoretically mobile subpopulation (74.3 +/-...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1993-01-11 00:00:00
abstract：:The in vitro vitamin K-dependent carboxylation of peptide- or protein-bound glutamate residues is generally studied in detergent-solubilized microsomes from rat or cow liver. Under the conditions usually employed, the efficiency of the carboxylation reaction is low (less than 1% of the carboxylatable residues is conve...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1987-02-03 00:00:00
abstract：:To study the effect of lymphocyte adhesion on the procoagulant activity of endothelial cells, we have stimulated HUVECs with interferon-gamma to upregulate adhesion molecules. Subsequent addition of lymphocytes induced the expression of tissue factor (TF) by HUVECs. Both CD4+ and CD8+ T-cells promoted this TF synthesi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
abstract：:Factor VIII procoagulant activity (F VIII:C) and factor VIII related antigen (F VIII R: Ag) were investigated in 35 patients with Argentine hemorrhagic fever. Since the results obtained in the three clinical forms of the disease were not significantly different, they were tabulated altogether. F VIII:C was low in earl...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1981-08-28 00:00:00
