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Laropiprant Attenuates EP3 and TP Prostanoid Receptor-Mediated Thrombus Formation
The use of the lipid lowering agent niacin is hampered by a frequent flush response which is largely mediated by prostaglandin (PG) D(2). Therefore, concomitant administration of the D-type prostanoid (DP) receptor antagonist laropiprant has been proposed to be a useful approach in preventing niacin...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411562/ https://www.ncbi.nlm.nih.gov/pubmed/22870195 http://dx.doi.org/10.1371/journal.pone.0040222 |
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author | Philipose, Sonia Konya, Viktoria Lazarevic, Mirjana Pasterk, Lisa M. Marsche, Gunther Frank, Sasa Peskar, Bernhard A. Heinemann, Akos Schuligoi, Rufina |
author_facet | Philipose, Sonia Konya, Viktoria Lazarevic, Mirjana Pasterk, Lisa M. Marsche, Gunther Frank, Sasa Peskar, Bernhard A. Heinemann, Akos Schuligoi, Rufina |
author_sort | Philipose, Sonia |
collection | PubMed |
description | The use of the lipid lowering agent niacin is hampered by a frequent flush response which is largely mediated by prostaglandin (PG) D(2). 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 PGD(2), which is a potent inhibitor of platelet aggregation, might pose the risk of atherothrombotic events in cardiovascular disease. In fact, we found that in vitro treatment of platelets with laropiprant prevented the inhibitory effects of PGD(2) on platelet function, i.e. platelet aggregation, Ca(2+) flux, 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, Ca(2+) flux, 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. 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. |
format | Online Article Text |
id | pubmed-3411562 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34115622012-08-06 Laropiprant Attenuates EP3 and TP Prostanoid Receptor-Mediated Thrombus Formation Philipose, Sonia Konya, Viktoria Lazarevic, Mirjana Pasterk, Lisa M. Marsche, Gunther Frank, Sasa Peskar, Bernhard A. Heinemann, Akos Schuligoi, Rufina PLoS One Research Article The use of the lipid lowering agent niacin is hampered by a frequent flush response which is largely mediated by prostaglandin (PG) D(2). 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 PGD(2), which is a potent inhibitor of platelet aggregation, might pose the risk of atherothrombotic events in cardiovascular disease. In fact, we found that in vitro treatment of platelets with laropiprant prevented the inhibitory effects of PGD(2) on platelet function, i.e. platelet aggregation, Ca(2+) flux, 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, Ca(2+) flux, 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. 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. Public Library of Science 2012-08-01 /pmc/articles/PMC3411562/ /pubmed/22870195 http://dx.doi.org/10.1371/journal.pone.0040222 Text en © 2012 Philipose et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Philipose, Sonia Konya, Viktoria Lazarevic, Mirjana Pasterk, Lisa M. Marsche, Gunther Frank, Sasa Peskar, Bernhard A. Heinemann, Akos Schuligoi, Rufina Laropiprant Attenuates EP3 and TP Prostanoid Receptor-Mediated Thrombus Formation |
title | Laropiprant Attenuates EP3 and TP Prostanoid Receptor-Mediated Thrombus Formation |
title_full | Laropiprant Attenuates EP3 and TP Prostanoid Receptor-Mediated Thrombus Formation |
title_fullStr | Laropiprant Attenuates EP3 and TP Prostanoid Receptor-Mediated Thrombus Formation |
title_full_unstemmed | Laropiprant Attenuates EP3 and TP Prostanoid Receptor-Mediated Thrombus Formation |
title_short | Laropiprant Attenuates EP3 and TP Prostanoid Receptor-Mediated Thrombus Formation |
title_sort | laropiprant attenuates ep3 and tp prostanoid receptor-mediated thrombus formation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411562/ https://www.ncbi.nlm.nih.gov/pubmed/22870195 http://dx.doi.org/10.1371/journal.pone.0040222 |
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