Structural identification of oxidized acyl-phosphatidylcholines that induce platelet activation

Oxidation of low-density lipoprotein (LDL) generates
proinflammatory and prothrombotic mediators that may play a crucial
role in cardiovascular and inflammatory diseases. In order to study
platelet-activating components of oxidized LDL
1-stearoyl-2-arachidonoyl-sn-glycero-3- phosphocholine, a
representative of the major phospholipid species in LDL, the
1-acyl-phosphatidylcholines (PC), was oxidized by CuCl2 and H2O2.
After separation by high-performance liquid chromatography, three
compounds were detected which induced platelet shape change at low
micromolar concentrations. Platelet activation by these compounds
was distinct from the pathways stimulated by platelet-activating
factor, lysophosphatidic acid, lyso-PC and thromboxane A(2), as
evidenced by the use of specific receptor antagonists. Further
analyses of the oxidized phospholipids by electrospray ionization
mass spectrometry structurally identified them as
1-stearoyl-2-azelaoyl-sn-glycero-3-phosphocholine (m/z 694; SAzPC),
1-stearoyl-2-glutaroyl-snglycero-3- phosphocholine (m/z 638; SGPC),
and 1-stearoyl-2-( 5-oxovaleroyl)-sn-glycero-3-phosphocholine (m/z
622; SOVPC). These observations demonstrate that novel 1-acyl-PC
which had previously been found to stimulate interaction of
monocytes with endothelial cells also induce platelet activation, a
central step in acute thrombogenic and atherogenic processes.
Copyright (C) 2005 S. Karger AG, Basel.