Paper Title
Effects Of Lysophosphatidylcholine And 7-Ketocholesterol On Human Endothelial Cells

Abstract
Increased levels of oxidized low-density lipoprotein (oxLDL)such as lysophosphatidylcholine (LPC) and 7-ketocholesterol (7-KC) may increase the risk of cardiovascular diseases such as atherosclerosis, thrombosis, stroke, myocardial infarction etc.This is possibly due to the toxicity of LPC and 7-KC towardvascular endothelial cells and stimulates vascular inflammation. However the toxicity of LPC and 7-KC on vascular endothelial cells isunclear. In this study, EAhy926 endothelial cells were exposed to LPC or 7-KC. Cellular cytotoxicity was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. IL-6protein expression was measured by western blotting. In some experiments, various inhibitors were added into endothelial cells for pretreatment before the addition of LPC or 7-KC, and then co-incubation for 24 hours. LPC and 7-KC showed marked cytotoxicity to endothelial cells at concentrations higher than 60 g/ml and 20 g/ml, respectively. Both LPC and 7-KC stimulated IL-6 protein expression of endothelial cells. LY294002 (a PI3K/Akt inhibitor) prevented the LPC- and 7-KC-induced IL-6 expression of endothelial cells.Moreover, betel leaf extract, eugenol and catechin potentially attenuated the LPC- and 7-KC-induced IL-6 expression of endothelial cells. These results indicate that oxLDLs such as LPC and 7-KC may be involved in the pathogenesis of atherosclerosis and vascular diseases by stimulation of IL-6 expression and vascular inflammation. These effects are related to activation of PI3K/Akt. Natural products such as betel leaf, eugenol and catechin may potentially prevent the oxLDL-induced toxicity to vascular endothelial cells. Understanding the toxic mechanisms of LPC and 7-KC are useful for future prevention and treatment atherosclerosis. (This study is supported by grants from Ministry of Science and Technology, Taiwan, ROC; Chang Gung Memorial Hospital, CMRP, Taiwan).