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.
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.
Ambrosch
Andreas
A
Institute of Medical Microbiology, Clinic of Nephrology, Otto-von Guericke University, Magdeburg, Germany. aambrosch@hotmail.com
Müller
Regina
R
Freytag
Claudia
C
Borgmann
Stefan
S
Kraus
Jürgen
J
Dierkes
Jutta
J
Neumann
Klaus H
KH
König
Wolfgang
W
D002448:Cell Adhesion; D002460:Cell Line; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007676:Kidney Failure, Chronic / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics; D010316:Particle Size; D010641:Phenotype; D018808:Transcription Factor AP-1 / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D020298:U937 Cells; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D008077:Lipoproteins, LDL; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1