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This article is part of the supplement: 18th Scientific Symposium of the Austrian Pharmacological Society (APHAR)

Open Access Meeting abstract

Laropiprant attenuates EP3 and TP prostanoid receptor-mediated thrombus formation

Sonia Philipose1, Viktória Kónya1, Mirjana Lazarević1, Lisa M Pasterk1, Gunther Marsche1, Sasa Frank2, Bernhard A Peskar1, Ákos Heinemann1* and Rufina Schuligoi1

Author affiliations

1 Institute of Experimental and Clinical Pharmacology, Medical University of Graz, 8010 Graz Austria

2 Institute of Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria

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Citation and License

BMC Pharmacology and Toxicology 2012, 13(Suppl 1):A14  doi:10.1186/2050-6511-13-S1-A14

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/2050-6511/13/S1/A14


Published:17 September 2012

© 2012 Philipose et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background

The use of the lipid-lowering agent niacin is hampered by a frequent flush response which is largely mediated by prostaglandin (PG) D2. Therefore, concomitant administration of the D-type prostanoid (DP) receptor antagonist laropiprant has been proposed to be a useful approach in preventing niacin-induced flush. However, antagonizing PGD2, which is a potent inhibitor of platelet aggregation, might pose the risk of atherothrombotic events in cardiovascular disease. Therefore, we investigated the effects of laropiorant on platelet function.

Methods

Platelet aggregation assays were performed ex vivo using a platelet aggregation analyser (Aggregometer II). Blood from healthy human donors was used to obtain platelet-rich plasma. The expression of P-selectin and activation of glycoprotein IIb/IIIa was examined using CD62P and PAC1 antibodies, respectively, by direct flow cytometry. In vitro thrombus formation was assessed by flowing whole blood on collagen-coated Cellix biochips at −30 dyn/cm2 using the Mirus nanopump.

Results

In vitro treatment of platelets with laropiprant prevented the inhibitory effects of PGD2 on platelet function, i.e. platelet aggregation, P-selectin expression, activation of glycoprotein IIb/IIIa and thrombus formation. In contrast, laropiprant did not prevent the inhibitory effects of acetylsalicylic acid or niacin on thrombus formation. At higher concentrations, laropiprant by itself attenuated platelet activation induced by thromboxane (TP) and E-type prostanoid (EP)-3 receptor stimulation, as demonstrated in assays of platelet aggregation, P-selectin expression, and activation of glycoprotein IIb/IIIa. Inhibition of platelet function exerted by EP4 or I-type prostanoid (IP) receptors was not affected by laropiprant.

Conclusions

These in vitro data suggest that niacin/laropiprant for the treatment of dyslipidemias might have a beneficial profile with respect to platelet function and thrombotic events in vascular disease.

Acknowledgements

S.P. was funded by the PhD Program Molecular Medicine of the Medical University of Graz. This study was supported by the Jubiläumsfonds of the Austrian National Bank (OeNB, grants 13487 and 14263) and the Austrian Science Fund (FWF; grants P22521-B18, P19473-B05, P21004-B02 and P22976-B18).