The tumour necrosis factor superfamily ligand APRIL (TNFSF13) is released upon platelet activation and expressed in atherosclerosis

Wiggo J. Sandberg; Kari Otterdal; Lars Gullestad; Bente Halvorsen; Asgrimur Ragnarsson; Stig S. Frøland; Jan K. Damås; Erik Øie; Pål Aukrust; Göran K. Hansson; Arne Yndestad

doi:10.1160/TH08-10-0665

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2009; 102(04): 704-710
DOI: 10.1160/TH08-10-0665

Platelets and Blood Cells

Schattauer GmbH

The tumour necrosis factor superfamily ligand APRIL (TNFSF13) is released upon platelet activation and expressed in atherosclerosis

Wiggo J. Sandberg

¹Research Institute for Internal Medicine, Rikshospitalet, Oslo University Hospital, Oslo, Norway

,

Kari Otterdal

¹Research Institute for Internal Medicine, Rikshospitalet, Oslo University Hospital, Oslo, Norway

⁴Faculty of Medicine, University of Oslo, Oslo, Norway

,

Lars Gullestad

²Department of Cardiology, Rikshospitalet, Oslo University Hospital, Oslo, Norway

⁴Faculty of Medicine, University of Oslo, Oslo, Norway

,

Bente Halvorsen

¹Research Institute for Internal Medicine, Rikshospitalet, Oslo University Hospital, Oslo, Norway

⁴Faculty of Medicine, University of Oslo, Oslo, Norway

,

Asgrimur Ragnarsson

²Department of Cardiology, Rikshospitalet, Oslo University Hospital, Oslo, Norway

,

Stig S. Frøland

¹Research Institute for Internal Medicine, Rikshospitalet, Oslo University Hospital, Oslo, Norway

³Section of Clinical Immunology and Infectious Diseases, Rikshospitalet, Oslo University Hospital, Oslo, Norway

⁴Faculty of Medicine, University of Oslo, Oslo, Norway

,

Jan K. Damås

¹Research Institute for Internal Medicine, Rikshospitalet, Oslo University Hospital, Oslo, Norway

³Section of Clinical Immunology and Infectious Diseases, Rikshospitalet, Oslo University Hospital, Oslo, Norway

,

Erik Øie

¹Research Institute for Internal Medicine, Rikshospitalet, Oslo University Hospital, Oslo, Norway

²Department of Cardiology, Rikshospitalet, Oslo University Hospital, Oslo, Norway

,

Pål Aukrust

¹Research Institute for Internal Medicine, Rikshospitalet, Oslo University Hospital, Oslo, Norway

³Section of Clinical Immunology and Infectious Diseases, Rikshospitalet, Oslo University Hospital, Oslo, Norway

⁴Faculty of Medicine, University of Oslo, Oslo, Norway

,

Göran K. Hansson

⁵Department of Medicine and Centre for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden

,

Arne Yndestad

¹Research Institute for Internal Medicine, Rikshospitalet, Oslo University Hospital, Oslo, Norway

⁴Faculty of Medicine, University of Oslo, Oslo, Norway

› Institutsangaben

Abstract

Summary

Activated platelets release a wide range of inflammatory mediators, including members of the tumour necrosis factor (TNF) superfamily (e.g. CD40 ligand [CD40L] and LIGHT). Such platelet-mediated inflammation could be involved in atherogenesis and plaque destabilisation. In the present study we investigated whether APRIL, another member of the TNF superfamily that has been detected in megakaryocytes, could be released from platelets upon activation. The release of APRIL was studied in thrombin receptor (SFLLRN) activated platelets, and the expression of APRIL was examined in plasma and within the atherosclerotic lesion in patients with carotid and coronary atherosclerosis. Upon SFLLRN activation, there was a gradual release of APRIL, reaching maximum after 90 minutes. While this pattern is similar to that of CD40L and LIGHT, the release of APRIL was quite differently regulated. Thus, prostaglandin E1,but not inhibitors of metal-dependent proteases and actin polymerisation or the lack of GP IIb/IIIa, blocks APRIL release in activated platelets. With relevance to atherogenesis, we found that patients with coronary artery disease (n=80) had raised plasma levels of APRIL as compared with controls (n=20), and APRIL immunoreactivity was detected in aggregated platelets within the ruptured plaque in patients with myocardial infarction and within macrophages in symptomatic carotid plaques. In conclusion, activated platelets release significant amounts of APRIL in a longlasting manner, differently regulated than the gradual release of other platelet-derived TNF superfamily ligands. The enhanced expression of APRIL in atherosclerotic disorders, both systemically and within the lesion, may suggest a potential involvement of APRIL in atherogenesis.

Keywords

Platelets - atherosclerosis - inflammation - tumor necrosis factor superfamily

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Referenzen

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