Lysophosphatidylcholine induces inflammatory activation of human coronary artery smooth muscle cells.
Lysophosphatidylcholine (LPC) is the major bioactive lipid component of oxidized LDL, thought to be responsible for many of the inflammatory effects of oxidized LDL described in both inflammatory and endothelial cells. Inflammation-induced transformation of vascular smooth muscle cells from a contractile phenotype to a proliferative/secretory phenotype is a hallmark of the vascular remodeling that is characteristic of atherogenesis; however, the role of LPC in this process has not been fully described. The present study tested the hypothesis that LPC is an inflammatory stimulus in coronary artery smooth muscle cells (CASMCs). In cultured human CASMCs, LPC stimulated time- and concentration-dependent release of arachidonic acid that was sensitive to phospholipase A2 and C inhibition. LPC stimulated the release of arachidonic acid metabolites leukotriene-B4 and 6-keto-prostaglandin F1alpha, within the same time course. LPC was also found to stimulate basic fibroblast growth factor release as well as stimulating the release of the cytokines GM-CSF, IL-6, and IL-8. Optimal stimulation of these signals was obtained via palmitic acid-substituted LPC species. Stimulation of arachidonic acid, inflammatory cytokines and growth factor release, implies that LPC might play a multifactorial role in the progression of atherosclerosis, by affecting inflammatory processes.
Aiyar
Nambi
N
Department of Vascular Biology and Thrombosis, Cardiovascular and Urogenital Center of Excellence for Drug Discovery, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA. Nambi_Aiyar-1@gsk.com
Disa
Jyoti
J
Ao
Zhaohui
Z
Ju
Haisong
H
Nerurkar
Sandhya
S
Willette
Robert N
RN
Macphee
Colin H
CH
Johns
Douglas G
DG
Douglas
Stephen A
SA
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D016718:Arachidonic Acid / Q000378:metabolism; D001095:Arachidonic Acids / Q000494:pharmacology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology* / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D007975:Leukotriene B4 / Q000096:biosynthesis; D008055:Lipids / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D010740:Phospholipases / Q000037:antagonists & inhibitors; D014316:Tritium
D001095:Arachidonic Acids; D016207:Cytokines; D008055:Lipids; D008244:Lysophosphatidylcholines; C081565:arachidonyltrifluoromethane; D014316:Tritium; D016222:Fibroblast Growth Factor 2; D007975:Leukotriene B4; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D010740:Phospholipases