Glycoxidized low-density lipoprotein enhances monocyte chemoattractant protein-1 mRNA expression in human umbilical vein endothelial cells: relation to lysophosphatidylcholine contents and inhibition by nitric oxide donor

Low-density lipoprotein (LDL) may undergo more glycation or oxidation in patients with diabetes mellitus than in nondiabetic subjects. We investigated whether glycoxidized LDL (goLDL) induces monocyte chemoattractant protein-1 (MCP-1) mRNA expression through activation of nuclear factor-kappaB (NFkappaB), and determined the effect of nitric oxide (NO) on MCP-1 mRNA expression in human umbilical vein endothelial cells (HUVEC). Oxidized (oxLDL) or goLDL enhanced MCP-1 mRNA expression in HUVEC, and preincubation with NOR3, a NO donor, abrogated such stimulation. goLDL increased NFkappaB-DNA binding activity in HUVEC and this effect was also suppressed by NOR3. We measured lysophosphatidylcholine (lyso-PC) contents in modified LDL using electrospray ionization liquid chromatography/mass spectrometry (LC/MS) to identify its molecular species. MCP-1 mRNA expression and NFkappaB activation correlated significantly with palmitoyl- and stearoyl-lyso-PC contents in LDL. Our results suggest that LDL modified by glycation and oxidation may contribute to the development of accelerated atherosclerosis in the presence of diabetes, a process that may be prevented by increased vascular NO availability.