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.