TY - JOUR
T1 - Lysophosphatidylcholine and secretory phospholipase A2 in vascular disease
T2 - Mediators of endothelial dysfunction and atherosclerosis
AU - Kougias, Panagiotis
AU - Chai, Hong
AU - Lin, Peter H.
AU - Lumsden, Alan B.
AU - Yao, Qizhi
AU - Chen, Changyi
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/1
Y1 - 2006/1
N2 - Lysophosphatidylcholine (LPC) is the major component of oxidized low density lipoprotein (ox-LDL) and it has the ability to initiate or amplify several steps in atherogenesis due to its ability to impair endothelium- dependent vasorelaxation, enhance endothelial proliferation and permeability, stimulate adhesion and activation of lymphocytes, initiate chemotaxis of macrophages, impair migration and proliferation in vascular smooth muscle cells (SMCs), and modify platelet aggregation and coagulation pathways. For many of the LPC-induced effects, protein kinase C-dependent pathways have been implicated. In addition, modulation of ion current activity in the cell membrane, binding to a specific oxLDL receptor or to G-protein coupled receptors, as well as amplification of a highly oxidative state have all been postulated as likely mediating mechanisms. Secretory phopholipase A 2-II (sPLA2-II) is one of the enzymes responsible for LPC production. sPLA2-II has been recently recognized as an independent risk factor for coronary artery disease. sPLA2-II favors the formation of bioactive lipids, stimulates SMC proliferation, activates macrophages enhancing lipid core formation and cytokine secretion, and binds to proteoglycans in the vessel wall matrix promoting lipid fusion and accumulation. The non-catalytic atherogenic effects of sPLA2-II are thought to be related to binding to an M-type receptor. Commonly used medications have been shown to decrease sPLA2-II activity generating a legitimate interest in the effects of the sPLA2-II pharmacologic antagonism. LPC and sPLA2-II are two very important mediators in atherosclerosis. Further research is warranted to clarify the cellular and molecular mechanisms that underlie their actions and to correlate in vitro data with clinical observations.
AB - Lysophosphatidylcholine (LPC) is the major component of oxidized low density lipoprotein (ox-LDL) and it has the ability to initiate or amplify several steps in atherogenesis due to its ability to impair endothelium- dependent vasorelaxation, enhance endothelial proliferation and permeability, stimulate adhesion and activation of lymphocytes, initiate chemotaxis of macrophages, impair migration and proliferation in vascular smooth muscle cells (SMCs), and modify platelet aggregation and coagulation pathways. For many of the LPC-induced effects, protein kinase C-dependent pathways have been implicated. In addition, modulation of ion current activity in the cell membrane, binding to a specific oxLDL receptor or to G-protein coupled receptors, as well as amplification of a highly oxidative state have all been postulated as likely mediating mechanisms. Secretory phopholipase A 2-II (sPLA2-II) is one of the enzymes responsible for LPC production. sPLA2-II has been recently recognized as an independent risk factor for coronary artery disease. sPLA2-II favors the formation of bioactive lipids, stimulates SMC proliferation, activates macrophages enhancing lipid core formation and cytokine secretion, and binds to proteoglycans in the vessel wall matrix promoting lipid fusion and accumulation. The non-catalytic atherogenic effects of sPLA2-II are thought to be related to binding to an M-type receptor. Commonly used medications have been shown to decrease sPLA2-II activity generating a legitimate interest in the effects of the sPLA2-II pharmacologic antagonism. LPC and sPLA2-II are two very important mediators in atherosclerosis. Further research is warranted to clarify the cellular and molecular mechanisms that underlie their actions and to correlate in vitro data with clinical observations.
KW - Atherosclerosis
KW - Endothelial cell
KW - Low density lipoprotein
KW - Lysophosphatidylcholine
KW - Macrophage
KW - Secretory phospholipase A
KW - Smooth muscle cell
KW - Vascular disease
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M3 - Review article
C2 - 16369478
AN - SCOPUS:30944447092
VL - 12
SP - RA5-RA16
JO - Medical Science Monitor
JF - Medical Science Monitor
SN - 1234-1010
IS - 1
ER -