Lysophosphatidylcholine induces inflammatory activation of human coronary artery smooth muscle cells

Abstract

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.

Differential lipid metabolism in monocytes and macrophages: influence of cholesterol loading

“…More importantly, lyso-PC levels are increased during the oxidation of LDL ( 22 ). Oxidized LDL (OxLDL) is important in the generation of foam cells and is involved in many aspects of the pathogenesis of atherosclerosis, and as lyso-PC is the major bioactive lipid component of OxLDL ( 11,23 ), it has been suggested that lyso-PC is the major factor contributing to the proatherogenic potential of OxLDL (24)(25)(26).…”

“…4). We found that there was an increased retention time on the test samples compared with the standards, also high levels of lyso-PC (18)(19)(20), and that lyso-PC is a major bioactive lipid component of OxLDL (24)(25)(26), we decided to test whether cholesterol or CE accumulation would have any effects on the metabolism of lyso-PC. To test this, we loaded THP-1 monocytes and macrophages with 14 C-lyso-PC alone, cholesterol/ 14 C-lyso-PC, and CE/ 14 C-lyso-PC micelles and incubated for 4 h and 24 h. Lipid and aqueous fractions were extracted from the cells and analyzed by TLC and autoradiography analysis.…”

Inflammation-Related Gene Expression by Lipid Oxidation Derived Products in the Progression of Atherosclerosis

“…Further, lyso-PC has also been found to stimulate the release of pro-inflammatory cytokines, such as IL-8 and IL-6, and of growth factors, such as bFGF, in human coronary artery SMCs [224]. Even nanomolar concentrations of lyso-PC are able to stimulate cytokine expression and monocyte recruitment [225].…”

Roles of ERK and NF-κB in Interleukin-8 Expression in Response to Heat Shock Protein 22 in Vascular Smooth Muscle Cells

“…IL-1β augments transcription of the IL-8 gene (Ho et al 2007), and IL-8 gene expression has been shown to be induced by tumor necrosis factor (Wang et al 1991) and lysophosphatidylcholine (Aiyar et al 2007), which is thought to play a major role in the proinflammatory effects of oxidized low density lipoprotein (oxLDL) (Steinberg et al 1989). However, mechanisms behind these molecules to up-regulate IL-8 have not yet been described.…”