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.
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kazuo
K
Sonoki
Mototaka
M
Yoshinari
Masanori
M
Iwase
Kenzo
K
Iino
Kojiro
K
Ichikawa
Shigehiro
S
Ohdo
Shun
S
Higuchi
Mitsuo
M
Iida
D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009574:Nitro Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism*
D018932:Chemokine CCL2; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D016328:NF-kappa B; D020030:Nitric Oxide Donors; D009574:Nitro Compounds; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; D004247:DNA; C061872:FK 409