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

• Published in: Metabolism, clinical and experimental clinical and experimental, 2002-09, Vol.51 (9), p.1135-1142
• Main Authors: Sonoki, Kazuo, Yoshinari, Mototaka, Iwase, Masanori, Iino, Kenzo, Ichikawa, Kojiro, Ohdo, Shigehiro, Higuchi, Shun, Iida, Mitsuo
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cells, Cultured; Chemokine CCL2 - genetics; Disorders of blood lipids. Hyperlipoproteinemia; DNA - metabolism; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Glycosylation; Humans; Lipoproteins, LDL - metabolism; Lipoproteins, LDL - pharmacology; Lysophosphatidylcholines - metabolism; Medical sciences; Metabolic diseases; NF-kappa B - physiology; Nitric Oxide Donors - pharmacology; Nitro Compounds - pharmacology; Oxidation-Reduction; RNA, Messenger - antagonists & inhibitors; RNA, Messenger - metabolism; Umbilical Veins - cytology; Umbilical Veins - metabolism
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1053/meta.2002.34703

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 (NF[kappa ]B), 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 NF[kappa ]B-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 NF[kappa ]B 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.