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Thromb Haemost 2014; 112(02): 332-341
DOI: 10.1160/TH13-12-1026
Platelets and Blood Cells
Schattauer GmbH

Apolipoprotein B100 danger-associated signal 1 (ApoBDS-1) triggers platelet activation and boosts platelet-leukocyte proinflammatory responses

Alice Assinger
1   Institute of Physiology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria
2   Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
,
Yajuan Wang
2   Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
3   Department of Geriatrics, Qilu Hospital, Shandong University, Jinan, China
,
Lynn M. Butler
2   Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
,
Göran K. Hansson
2   Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
,
Zhong-qun Yan
2   Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
,
Cecilia Söderberg-Nauclér
2   Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
,
Daniel F. J. Ketelhuth
2   Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
› Author Affiliations Financial support: This study was supported by the CERIC Linnaeus Program (Center of Excellence for Research on Inflammation and Cardiovascular disease—349–2007–8703), the Swedish Research Council-Medicine (project grants 521–2009–4203, 521–2012–2440), the Swedish Heart-Lung Foundation, Karolinska Institute Cardiovascular Program Career Development Grant, the Swedish Foundation for Strategic Research (SSF), Vinnova Foundation, Åke Wibergs Stiftelse, Stiftelsen för Gamla Tjänarinnor, Stiftelsen för alders sjukdomar vid Karolinska Institutet, Stiftelsen Professor Nanna Svartz fond, KI fond, European Union projects (Molstroke, AtheroRemo) and the Austrian Science Fond (FWF–P24978). YW is supported by the China Scholarship Council (CSC).
Further Information

Publication History

Received: 16 December 2013

Accepted after major revision: 20 March 2014

Publication Date:
04 December 2017 (online)

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Summary

Low-density lipoproteins (LDL), occurring in vivo in both their native and oxidative form, modulate platelet function and thereby contribute to atherothrombosis. We recently identified and demonstrated that ‘ApoB100 danger-associated signal 1’ (ApoBDS-1), a native peptide derived from Apolipoprotein B-100 (ApoB100) of LDL, induces inflammatory responses in innate immune cells. Platelets are critically involved in the development as well as in the lethal consequences of atherothrombotic diseases, but whether ApoBDS-1 has also an impact on platelet function is unknown. In this study we examined the effect of ApoBDS-1 on human platelet function and platelet-leukocyte interactions in vitro. Stimulation with ApoBDS-1 induced platelet activation, degranulation, adhesion and release of proinflammatory cytokines. ApoBDS-1-stimulated platelets triggered innate immune responses by augmenting leukocyte activation, adhesion and transmigration to/through activated HUVEC monolayers, under flow conditions. These platelet-activating effects were sequence-specific, and stimulation of platelets with ApoBDS-1 activated intracellular signalling pathways, including Ca2+, PI3K/Akt, PLC, and p38– and ERKMAPK. Moreover, our data indicates that ApoBDS-1-induced platelet activation is partially dependent of positive feedback from ADP on P2Y1 and P2Y12, and TxA2. In conclusion, we demonstrate that ApoBDS-1 is an effective platelet agonist, boosting platelet-leukocyte’s proinflammatory responses, and potentially contributing to the multifaceted inflammatory-promoting effects of LDL in the pathogenesis of atherothrombosis.

Keywords

Platelets - LDL - ApoB - inflammation - and atherosclerosis

 

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