Cholesterol enrichment of arterial-smooth muscle cells upregulates cytokine-induced nitric oxide synthesis Academic Article uri icon


MeSH Major

  • Aorta, Thoracic
  • Cholesterol
  • Cytokines
  • Interferon-gamma
  • Muscle, Smooth, Vascular
  • Nitric Oxide


  • Endothelium-derived relaxing factor/nitric oxide (EDRF/NO) is produced by the vascular wall and is a key modulator of vascular tone and blood pressure. NO is also produced by vascular smooth muscle (VSMC) where it can inhibit proliferation. Since cytokine-activated VSMC proliferation is a major event in the development of atherosclerosis, we investigated the influence of cholesterol (CE)-enrichment of VSMC on cytokine-induced NO synthesis. Treatment of VSMC with native LDL for one week did not promote CE-accretion or alter NO production following exposure to endotoxin (LPS). In contrast, CE-enrichment by cationized LDL augmented LPS-induction of NO synthesis 2-5-fold. While TNF-alpha promoted little NO synthesis in control VSMC, it was very potent after CE-enrichment. Similarly, CE-enrichment augmented IL-1 alpha-induced NO synthesis. However, CE-enrichment did not affect the synergistic induction of NO synthesis by cytokines in combination with IFN-gamma. Our findings suggest that CE-enrichment of VSMC upregulates signal transduction pathways which mediate cytokine and LPS induction of NO synthase activity.

publication date

  • January 1993



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1006/bbrc.1993.1190

PubMed ID

  • 8447815

Additional Document Info

start page

  • 103

end page

  • 9


  • 191


  • 1