Structural identification of oxidized acyl-phosphatidylcholines that induce platelet activation
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Structural identification of oxidized acyl-phosphatidylcholines that induce platelet activation. / Göpfert, Matthias S; Siedler, Frank; Siess, Wolfgang; Sellmayer, Alois.
In: J VASC RES, Vol. 42, No. 2, 2005, p. 120-32.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Structural identification of oxidized acyl-phosphatidylcholines that induce platelet activation
AU - Göpfert, Matthias S
AU - Siedler, Frank
AU - Siess, Wolfgang
AU - Sellmayer, Alois
N1 - Copyright 2005 S. Karger AG, Basel.
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
KW - Blood Platelets
KW - Calcium
KW - Cell Shape
KW - Chromatography, High Pressure Liquid
KW - Cytosol
KW - Humans
KW - Molecular Structure
KW - Osmolar Concentration
KW - Oxidation-Reduction
KW - Phosphatidylcholines
KW - Platelet Activation
KW - Spectrometry, Mass, Electrospray Ionization
U2 - 10.1159/000083461
DO - 10.1159/000083461
M3 - SCORING: Journal article
C2 - 15665547
VL - 42
SP - 120
EP - 132
IS - 2
ER -
