The plaque lipid lysophosphatidic acid stimulates platelet activation and platelet-monocyte aggregate formation in whole blood

Involvement of P2Y 1 and P2Y12 receptors

Nadine Haserück, Wolfgang Erl, Dharmendra Pandey, Gabor Tigyi, Philippe Ohlmann, Catherine Ravanat, Christian Gachet, Wolfgang Siess

Research output: Contribution to journalArticle

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Abstract

Despite the fact that lysophosphatidic acid (LPA) has been identified as a main platelet-activating lipid of mildly oxidized low-density lipoprotein (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 fatty acid) 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 blood was donor dependent. It could be completely blocked by apyrase and antagonists of the platelet adenosine diphosphate (ADP) receptors P2Y1 P2Y 12. 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 P2Y 1 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 P2Y 12 receptors might be useful preventing LPA-elicited thrombus formation in patients with cardiovascular diseases.

Original languageEnglish (US)
Pages (from-to)2585-2592
Number of pages8
JournalBlood
Volume103
Issue number7
DOIs
StatePublished - Apr 1 2004

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Platelet Activation
Platelets
Monocytes
Blood
Blood Platelets
Chemical activation
Lipids
Platelet Aggregation
Agglomeration
Platelet-Rich Plasma
Blood Donors
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
lysophosphatidic acid
Plasmas
Adenosine Diphosphate
Apyrase
Purinergic P2Y1 Receptors
Aspirin
Serotonin

All Science Journal Classification (ASJC) codes

  • Hematology

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The plaque lipid lysophosphatidic acid stimulates platelet activation and platelet-monocyte aggregate formation in whole blood : Involvement of P2Y 1 and P2Y12 receptors. / Haserück, Nadine; Erl, Wolfgang; Pandey, Dharmendra; Tigyi, Gabor; Ohlmann, Philippe; Ravanat, Catherine; Gachet, Christian; Siess, Wolfgang.

In: Blood, Vol. 103, No. 7, 01.04.2004, p. 2585-2592.

Research output: Contribution to journalArticle

Haserück, Nadine ; Erl, Wolfgang ; Pandey, Dharmendra ; Tigyi, Gabor ; Ohlmann, Philippe ; Ravanat, Catherine ; Gachet, Christian ; Siess, Wolfgang. / The plaque lipid lysophosphatidic acid stimulates platelet activation and platelet-monocyte aggregate formation in whole blood : Involvement of P2Y 1 and P2Y12 receptors. In: Blood. 2004 ; Vol. 103, No. 7. pp. 2585-2592.
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