Atherogenic role of lysophosphatidylcholine in low-density lipoprotein modified by phospholipase A₂ and in diabetic patients: Protection by nitric oxide donor☆

Abstract 

The aim of our study was to investigate the atherogenic role of lysophosphatidylcholine (lyso-PC) in low-density lipoprotein (LDL) under diabetic environment. Expression of monocyte chemoattractant protein-1 (MCP-1) mRNA and nuclear factor-kappa B (NF-κB)–DNA binding activity were determined in human umbilical vein endothelial cells (HUVEC) incubated with native or glycoxidized LDL, LDL modified by phospholipase A₂ (PLA₂) and LDL isolated from diabetic patients. Lyso-PC contents in LDL were measured using electrospray ionization–liquid chromatography/mass spectrometry (ESI-LC/MS). Lyso-PC contents were higher in glycoxidized LDL and PLA₂-treated LDL compared with native LDL. Glycoxidized LDL and enrichment of lyso-PC by PLA₂ treatment resulted in upregulation of MCP-1 mRNA expression through increased NF-κB activity in HUVEC. Moreover, LDL isolated from diabetics contained more lyso-PC than that from nondiabetic subjects, and induced higher MCP-1 mRNA expression and NF-κB activity in HUVEC. In both in vitro and human studies, palmitoyl- and stearoyl-lyso-PC contents correlated with MCP-1 expression and NF-κB activity. Preincubation with 4-ethyl-2-hydroxyimino-5-nitro-3-hexenamide, a NO donor, abrogated increased expression of MCP-1 mRNA and high NF-κB activity induced by PLA₂-treated LDL and by LDL isolated from diabetic patients. Our results suggest that lyso-PC contents in LDL play an important role in atherogenesis under diabetic condition, which could be prevented by increased availability of vascular NO. Copyright 2003, Elsevier Science (USA). All rights reserved.

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