Lysophosphatidic acid-independent platelet activation by low-density lipoprotein.
Mildly oxidized low-density lipoprotein activates platelets through lysophosphatidic acid (LPA). Hence, the platelet-activating properties attributed to native low-density lipoprotein (nLDL) might be caused by LPA contamination. We show that nLDL enhances thrombin receptor-activating peptide (TRAP)-induced fibrinogen binding to alpha(IIb)beta(3). The LPA receptor blocker N-palmitoyl-L-serine-phosphoric acid did not affect nLDL-enhanced fibrinogen binding induced by TRAP, but reduced TRAP-induced binding. cAMP and inhibitors of protein kinase C and Ca(2+) rises completely blocked ligand binding by TRAP and nLDL/TRAP. Inhibitors of p38(MAPK) and ADP secretion interfered only partially. Blockade of Rho-kinase increased ligand binding 2-3-fold. We conclude that nLDL enhances TRAP-induced fibrinogen binding independent of LPA.
Korporaal
S J
SJ
Department of Haematology, Laboratory Thrombosis and Haemostasis, Institute for Biomembranes, University Medical Center Utrecht, The Netherlands. j.a.korporaal@lab.azu.nl
Relou
I A
IA
van Rijn
H J
HJ
Akkerman
J W
JW
D000244:Adenosine Diphosphate / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008246:Lysophospholipids / Q000378:metabolism*; D010168:Palmitates / Q000378:metabolism / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010768:Phosphoserine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D015539:Platelet Activation / Q000502:physiology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D015398:Signal Transduction; D054460:rho-Associated Kinases
D047908:Intracellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL; D008246:Lysophospholipids; C101516:N-palmitoylserine phosphoric acid; D010168:Palmitates; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; C086309:thrombin receptor peptide SFLLRNP; D010768:Phosphoserine; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D000242:Cyclic AMP; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D002118:Calcium