Abstract:
:High mobility group box 1 (HMGB1) acts as both a nuclear protein that regulates gene expression, as well as a pro-inflammatory alarmin that is released from necrotic or activated cells. Recently, HMGB1-expression in human atherosclerotic plaques was identified. Therapeutic blockade of HMGB1 reduced the development of diet-induced atherosclerosis in ApoE knockout mice. Thus, we hypothesised an interaction between HMGB1 and activated platelets. Binding of recombinant HMGB1 to platelets was assessed by flow cytometry. HMGB1 bound to thrombin-activated human platelets (MFI 2.49 vs 25.01, p=0.0079). Blood from wild-type, TLR4 and RAGE knockout mice was used to determine potential HMGB1 receptors on platelets. HMGB1 bound to platelets from wild type C57Bl6 (MFI 2.64 vs 20.3, p< 0.05), and TLR4-/- mice (MFI 2.11 vs 25.65, p< 0.05) but failed to show binding to platelets from RAGE-/- mice (p > 0.05). RAGE expression on human platelets was detected by RT-PCR with mRNA extracted from highly purified platelets and confirmed by Western blot and immunofluorescence microscopy. Platelet activation increased RAGE surface expression (MFI 4.85 vs 6.74, p< 0.05). Expression of HMGB1 in human coronary artery thrombi was demonstrated by immunohistochemistry and revealed high expression levels. Platelets bind HMGB1 upon thrombin-induced activation. Platelet specific expression of RAGE could be detected at the mRNA and protein level and is involved in the binding of HMGB1. Furthermore, platelet activation up-regulates platelet surface expression of RAGE. HMGB1 is highly expressed in platelet-rich human coronary artery thrombi pointing towards a central role for HMGB1 in atherothrombosis, thereby suggesting the possibility of platelet targeted anti-inflammatory therapies for atherothrombosis.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Ahrens I,Chen YC,Topcic D,Bode M,Haenel D,Hagemeyer CE,Seeba H,Duerschmied D,Bassler N,Jandeleit-Dahm KA,Sweet MJ,Agrotis A,Bobik A,Peter Kdoi
10.1160/TH14-12-1073subject
Has Abstractpub_date
2015-11-01 00:00:00pages
994-1003issue
5eissn
0340-6245issn
2567-689Xpii
14-12-1073journal_volume
114pub_type
杂志文章abstract::A simple collagen binding assay (CBA) for measuring activity of the von Willebrand factor cleaving protease in clinical samples is described, and results of fifty masked plasmapheresis samples rom patients with TTP/HUS and other diseases are presented. There was 97.5% concordance between the CBA and a multimer gel ass...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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更新日期:2002-10-01 00:00:00
abstract::Inflammation and thrombosis, two processes influencing each other, are involved in the pathogenesis of cerebrovascular disease. We showed that in patients with acute ischaemic stroke circulating platelets are activated and exhausted. To identify whether activated haemostasis might be cause or effect, we investigated t...
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doi:10.1160/TH09-09-0620
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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:1980-02-29 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1055/s-0039-1693740
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abstract::Heparin is one of the oldest biological medicines, and has an established place in the prevention and treatment of venous thrombosis. Low-molecular-weight heparins (LMWH) have been developed by several manufacturers and have advantages in terms of pharmacokinetics and convenience of administration. They have been show...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
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更新日期:2008-05-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH12-06-0436
更新日期:2012-12-01 00:00:00
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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:1999-07-01 00:00:00
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journal_title:Thrombosis and haemostasis
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更新日期:2002-10-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH05-08-0571
更新日期:2006-03-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1996-08-01 00:00:00
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journal_title:Thrombosis and haemostasis
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journal_title:Thrombosis and haemostasis
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doi:10.1160/TH03-10-0618
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1981-06-30 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2007-04-01 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:
更新日期:2009-05-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-02-0086
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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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abstract:: ...
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,评审
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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,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
doi:
更新日期:1998-04-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1986-06-30 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1991-11-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
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,多中心研究
doi:10.1160/TH08-12-0842
更新日期:2009-09-01 00:00:00