Small-sized low-density lipoproteins of subclass B from patients with end-stage renal disease effectively augment tumor necrosis factor-alpha-induced adhesive properties in human endothelial cells

Am J Kidney Dis. 2002 May;39(5):972-84. doi: 10.1053/ajkd.2002.32771.


Increased prevalence of small-sized low-density lipoprotein (LDL) subclass B (diameter < 25.5 nm) possibly is involved in the multifactorial process of cardiovascular disease in patients with end-stage renal disease. Given these epidemiological observations, mechanisms underlying the combined effect of a proinflammatory insult and LDL of different subclasses (subclass A, diameter > 25.5 nm, and subclass B) in a cellular model were investigated. For this, human umbilical vein endothelial cells were preexposed to LDL, then stimulated with tumor necrosis factor-alpha (TNF-alpha). Modulatory effects of LDL phenotypes on the activation of adhesion molecules, monocyte adherence, and transcriptional activity of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) were investigated. Our data show that subclass B LDLs were metabolized through nonspecific scavenger receptors and specific LDL-receptor pathways in endothelial cells. Furthermore, LDL subclass B in comparison to subclass A more effectively enhanced monocyte recruitment and adhesive properties of endothelial cells in response to TNF-alpha. These effects appeared not to be mediated by oxidative stress-responsive NF-kappaB because modulation of this transcription factor by LDL was moderate and similar for both LDL phenotypes. Conversely, effects of LDL subclass B were considered to be caused by augmented AP-1 binding activity. In conclusion, the present model provides new clues in atherogenic mechanisms of small-sized LDLs, which sensitize vascular cells to inflammatory signals more effectively than normal-sized LDLs.

MeSH terms

  • Cell Adhesion
  • Cell Line
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiology*
  • Female
  • Humans
  • Hypertriglyceridemia / blood
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Kidney Failure, Chronic / blood*
  • Lipoproteins, LDL / blood
  • Lipoproteins, LDL / classification*
  • Lipoproteins, LDL / genetics
  • Lipoproteins, LDL / metabolism
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • NF-kappa B / genetics
  • Particle Size
  • Phenotype
  • Transcription Factor AP-1 / genetics
  • Transcription, Genetic / physiology
  • Tumor Necrosis Factor-alpha / physiology*
  • U937 Cells
  • Umbilical Veins
  • Vascular Cell Adhesion Molecule-1 / biosynthesis


  • Lipoproteins, LDL
  • NF-kappa B
  • Transcription Factor AP-1
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1