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 CuCl(2) and H(2)O(2). 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, lyso-phosphatidic 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-sn- glycero-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.
Göpfert
Matthias S
MS
Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Klinikum der Universität Munchen, München, Deutschland.
Siedler
Frank
F
Siess
Wolfgang
W
Sellmayer
Alois
A
D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015539:Platelet Activation; D021241:Spectrometry, Mass, Electrospray Ionization
C500236:1-stearoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine; C500234:1-stearoyl-2-azelaoyl-sn-glycero-3-phosphocholine; C500235:1-stearoyl-2-glutaroyl-sn-glycero-3-phosphocholine; D010713:Phosphatidylcholines; C043644:1-stearoyl-2-arachidonylphosphatidylcholine; D002118:Calcium