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Blood, 1 April 2004, Vol. 103, No. 7, pp. 2585-2592. Prepublished online as a Blood First Edition Paper on November 26, 2003; DOI 10.1182/blood-2003-04-1127. This Article Full Text (PDF) All Versions of this Article: 2003-04-1127v1 103/7/2585    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Haserueck, N. Articles by Siess, W. Search for Related Content PubMed PubMed Citation Articles by Haserueck, N. Articles by Siess, W. Social Bookmarking                   What's this? Submitted April 11, 2003 Accepted November 5, 2003 The plaque lipid lysophosphatidic acid stimulates platelet activation and platelet-monocyte aggregate formation in whole blood: involvement of P2Y1 and P2Y12 receptors Nadine Haserueck, Wolfgang Erl, Dharmendra Pandey, Gabor Tigyi, Philippe Ohlmann, Catherine Ravanat, Christian Gachet, and Wolfgang Siess* Institute for Prevention of Cardiovascular Diseases, University of Munich, Munich, Germany INSERM, Unite 311, EFS-Alsace, Strasbourg, France Department of Physiology, The University of Tennessee Health Sciences Center, Memphis, TN, USA * Corresponding author; email: wolfgang.siess{at}klp.med.uni-muenchen.de. Despite that lysophosphatidic acid (LPA) has been identified as a main platelet-activating lipid of mildly-oxidized LDL and human atherosclerotic lesions, it remains unknown, whether it is capable of activating platelets in blood. We found that LPA at concentrations slightly above plasma levels induces platelet shape change, aggregation and platelet-monocyte aggregate formation in blood. 1-Alkyl-LPA(16:0) was almost 20-fold more potent than 1-acyl-LPA(16:0). LPA directly induced platelet shape change in blood and platelet-rich plasma obtained from all blood donors. However, LPA-stimulated platelet aggregation in whole blood was donor-dependent. It could be completely blocked by apyrase and antagonists of the platelet ADP-receptors P2Y1 and P2Y12. These substances also inhibited LPA-induced aggregation of platelet-rich plasma, and aggregation and serotonin secretion of washed platelets. These results indicate a central role for ADP-mediated P2Y1 and P2Y12 receptor activation in supporting LPA-induced platelet aggregation. Platelet aggregation and platelet-monocyte aggregate formation stimulated by LPA was insensitive to inhibition by aspirin. We conclude that LPA at concentrations approaching those found in vivo can induce platelet shape change, aggregation and platelet-monocyte aggregate formation in whole blood and suggest that antagonists of platelet P2Y1 and P2Y12 receptors might be useful preventing LPA-elicited thrombus formation in patients with cardiovascular diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. R. Williams, A. L. Khandoga, P. Goyal, J. I. Fells, D. H. Perygin, W. Siess, A. L. Parrill, G. Tigyi, and Y. Fujiwara Unique Ligand Selectivity of the GPR92/LPA5 Lysophosphatidate Receptor Indicates Role in Human Platelet Activation J. Biol. Chem., June 19, 2009; 284(25): 17304 - 17319. [Abstract] [Full Text] [PDF] Z. Pamuklar, L. Federico, S. Liu, M. Umezu-Goto, A. Dong, M. Panchatcharam, Z. Fulerson, E. Berdyshev, V. Natarajan, X. Fang, et al. 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