HMGB1 binds to activated platelets via the receptor for advanced glycation end products and is present in platelet rich human coronary artery thrombi

Ahrens, Ingo, Chen, Yung-Chih, Topcic, Danijal, Bode, Michael, Haenel, David, Hagemeyer, Christoph E., Seeba, Hannah, Duerschmied, Daniel, Bassler, Nicole, Jandeleit-Dahm, Karin A., Sweet, Matthew J., Agrotis, Alex, Bobik, Alex and Peter, Karlheinz (2015) HMGB1 binds to activated platelets via the receptor for advanced glycation end products and is present in platelet rich human coronary artery thrombi. Thrombosis and Haemostasis, 114 5: 994-1003. doi:10.1160/TH14-12-1073

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Author Ahrens, Ingo
Chen, Yung-Chih
Topcic, Danijal
Bode, Michael
Haenel, David
Hagemeyer, Christoph E.
Seeba, Hannah
Duerschmied, Daniel
Bassler, Nicole
Jandeleit-Dahm, Karin A.
Sweet, Matthew J.
Agrotis, Alex
Bobik, Alex
Peter, Karlheinz
Title HMGB1 binds to activated platelets via the receptor for advanced glycation end products and is present in platelet rich human coronary artery thrombi
Journal name Thrombosis and Haemostasis   Check publisher's open access policy
ISSN 0340-6245
Publication date 2015-07-23
Year available 2015
Sub-type Article (original research)
DOI 10.1160/TH14-12-1073
Open Access Status Not yet assessed
Volume 114
Issue 5
Start page 994
End page 1003
Total pages 10
Place of publication Stuttgart, Germany
Publisher Schattauer GmbH
Collection year 2016
Language eng
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.
Keyword HMGB1
Platelets
RAGE
ACS
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
 
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