Abstract:
:Deep-vein thrombosis (DVT) is a common condition that often leads to pulmonary thromboembolism (VTE) and death. The role of prostaglandin-endoperoxide synthase (PTGS)2 in arterial thrombosis has been well established, whereas its impact in venous thrombosis remains unclear. Here, we showed that PTGS2 deletion predisposes to venous thrombosis as suggested by greater clot firmness and clot elasticity, by higher plasma levels of functional fibrinogen, factor VIII and PAI-1 activity, and proved by bigger thrombi detected after inferior vena cava ligation (IVCL) compared to WT mice. PTGS2-/- thrombi have greater fibrin content, higher number of F4/80+, TF+ and ANXA2+ cells, and lower S100A10+ cells. Remarkably, monocyte depletion reduced thrombus size in mutant mice, suggesting an important role of PTGS2-/- monocytes in this experimental setting. Interestingly, PTGS2 deletion reduced membrane ANXA2, and total S100A10, promoted assembly of ANXA2/p50NF-kB complex and its nuclear accumulation, and induced TF in peritoneal macrophages, whereas ANXA2 silencing decreased dramatically TF. Finally, Carbaprostacyclin treatment prevented venous thrombus formation induced by IVCL in mutant mice, reduced the ANXA2 binding to p50NF-kB subunit and its nuclear trafficking, and decreased TF in PTGS2-/- macrophages. PTGS2 deletion, changing the natural distribution of ANXA2 in monocytes/macrophages, increases TF expression and activity predisposing to venous thrombosis. Interestingly, Carbaprostacyclin treatment, inhibiting nuclear ANXA2 trafficking, controls monocyte TF activity and prevents DVT occurrence. Our data are of help in elucidating the mechanisms by which PTGS2 inhibition increases DVT risk, and suggest a new role for ANXA2 in venous thrombosis.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Amadio P,Tarantino E,Sandrini L,Tremoli E,Barbieri SSdoi
10.1160/TH16-12-0968subject
Has Abstractpub_date
2017-07-26 00:00:00pages
1486-1497issue
8eissn
0340-6245issn
2567-689Xpii
16-12-0968journal_volume
117pub_type
杂志文章abstract::The alphaII(b)beta3 integrin and FcgammaRII receptors mediate, respectively, platelet adhesion and spreading on fibrinogen and immunoglobulin (IgG) coated surfaces. Platelet adhesion to fibrinogen resulted in a partial conversion of the faster to the slower migrating (phosphorylated) form of Ca(+2)-sensitive cytosolic...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-04-01 00:00:00
abstract::Bacterial pneumonia, the most common cause of sepsis, is associated with activation of coagulation. Factor XI (FXI), the key component of the intrinsic pathway, can be activated via factor XII (FXII), part of the contact system, or via thrombin. To determine whether intrinsic coagulation is involved in host defence du...
journal_title:Thrombosis and haemostasis
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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abstract::Following the initial report of the clinical use of plasminogen activators (PAs) in cerebrovascular thrombosis in 1958, interest in the efficacy of this approach accelerated only when the need for acute intervention in stroke was recognized. The use of PAs in acute ischemic stroke is based on the observation that appr...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1997-07-01 00:00:00
abstract::To assess whether plasminogen activator inhibitor 1 (PAI-1) activity is elevated in the progeny of young coronary men, 193 young subjects were recruited and divided into two groups. Group A consisted of 104 children whose fathers had suffered a myocardial infarction before the age of 55 ("cases"). Eighty-nine young su...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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更新日期:1996-09-01 00:00:00
abstract::Arterial stenosis results in a complex pattern of blood flow containing an extremely fast flow in the throat of stenosis and a post-stenosis low flow. The fast flow generates high shear stress that has been demonstrated in vitro to activate and aggregate platelets. One potential problem of these in vitro studies is th...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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更新日期:2002-11-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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更新日期:1994-07-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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更新日期:1998-06-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
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journal_title:Thrombosis and haemostasis
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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更新日期:2008-08-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH14-11-0981
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journal_title:Thrombosis and haemostasis
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0039-1679939
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,meta分析
doi:10.1160/TH16-08-0595
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
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journal_title:Thrombosis and haemostasis
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究,随机对照试验
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-02-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-09-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-05-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
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journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章
doi:
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journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1998-11-01 00:00:00