Abstract:
:Overexpression of plasminogen activator inhibitor-1 (SERPINE1, PAI-1), the major physiological inhibitor of pericellular plasmin generation, is a significant causative factor in the progression of vascular disorders (e.g. arteriosclerosis, thrombosis, perivascular fibrosis) as well as a biomarker and a predictor of cardiovascular-disease associated mortality. PAI-1 is a temporal/spatial regulator of pericellular proteolysis and ECM accumulation impacting, thereby, vascular remodeling, smooth muscle cell migration, proliferation and apoptosis. Within the specific context of TGF-beta1-initiated vascular fibrosis and neointima formation, PAI-1 is a member of the most prominently expressed subset of TGF-beta1-induced transcripts. Recent findings implicate EGFR/pp60c-src-->MEK/ERK1/2 and Rho/ROCK-->SMAD2/3 signaling in TGF-beta1-stimulated PAI-1 expression in vascular smooth muscle cells. The EGFR is a direct upstream regulator of MEK/ERK1/2 while Rho/ROCK modulate both the duration of SMAD2/3 phosphorylation and nuclear accumulation. E-box motifs (CACGTG) in the PE1/PE2 promoter regions of the human PAI-1 gene, moreover, are platforms for a MAP kinase-directed USF subtype switch (USF-1-->USF-2) in response to growth factor addition suggesting that the EGFR-->MEK/ERK axis impacts PAI-1 expression, at least partly, through USF-dependent transcriptional controls. This paper reviews recent data suggesting the essential cooperativity among the EGFR-->MAP kinase cascade, the Rho/ROCK pathway and SMADs in TGF-beta1-initiated PAI-1 expression. The continued clarification of mechanistic controls on PAI-1 transcription may lead to new targeted therapies and clinically-relevant options for the treatment of vascular diseases in which PAI-1 dysregulation is a major underlying pathogenic feature.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Samarakoon R,Higgins PJsubject
Has Abstractpub_date
2008-12-01 00:00:00pages
976-83issue
6eissn
0340-6245issn
2567-689Xpii
08120976journal_volume
100pub_type
杂志文章,评审abstract::Recent clinical studies have shown that the interruption of platelet function appears to be effective for treatment of coronary occlusive diseases. For this purpose, a Fab fragment of humanized anti-platelet glycoprotein (GP) IIb/IIIa monoclonal antibody (YM 337) that exhibited an in vivo antithrombotic effect without...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章
doi:
更新日期:1998-07-01 00:00:00
abstract::The clinical benefits of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been shown in many trials. However, the mode of action of heparin has not been fully elucidated. Thus, we wanted to study the effects of UFH and LMWH in vivo by measuring coagulation activation markers in blood obtained ...
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:1994-12-01 00:00:00
abstract::In proliferative retinopathies, like proliferative diabetic retinopathy and retinopathy of prematurity (ROP), the hypoxia response is sustained by the failure of the retina to revascularise its ischaemic areas. Non-resolving retina ischaemia/hypoxia results in upregulation of pro-angiogenic factors and pathologic neov...
journal_title:Thrombosis and haemostasis
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abstract::Prolonged immobilization and advanced age are considered to be important risk factors for venous thromboembolism (VTE). Nevertheless, the need for VTE prophylaxis in long-term bedridden patients is not known. To assess whether very prolonged immobilization (i.e. over three months) carries an increased risk for clinica...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH03-07-0481
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abstract::Plasminogen activator inhibitor 1 (PAI-1) is the main inhibitor of tissue-type and urokinase-type plasminogen activators (t/uPA) and plays an important role in fibrinolysis. Inhibition of PAI-1 activity prevents thrombosis and accelerates fibrinolysis, indicating that PAI-1 inhibitors may be used as effective antithro...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH16-11-0891
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1988-08-30 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2007-12-01 00:00:00
abstract::Alpha-enolase is an ubiquitous cytoplasmic glycolytic enzyme which also exhibits cell surface mediated functions and a structural role in the lens of some species. An alpha-enolase related molecule (alpha-ERM) is present on the surfaces of neutrophils, monocytes and monocytoid cells and has the capacity to specificall...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-09-01 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: 杂志文章
doi:10.1160/TH15-09-0749
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH17-07-0478
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abstract::The binding of the urokinase plasminogen activator (uPA) to its receptor (uPAR) regulates cell adhesion, surface proteolysis, chemotaxis and cell extravasation in a number of experimental systems. Recent evidences have suggested that uPAR can by itself mediate chemotaxis of human monocytes and cause profound changes i...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1999-09-01 00:00:00
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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
pub_type: 杂志文章
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH16-04-0305
更新日期:2016-09-27 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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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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journal_title:Thrombosis and haemostasis
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doi:10.1160/TH-09-04-0224
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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:1995-09-01 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
doi:
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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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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