Role of hydrogen sulfide in the development of atherosclerotic lesions in apolipoprotein E knockout mice

Arterioscler Thromb Vasc Biol. 2009 Feb;29(2):173-9. doi: 10.1161/ATVBAHA.108.179333. Epub 2008 Nov 6.

Abstract

Objective: We explored the effect of hydrogen sulfide (H(2)S) on atherosclerotic progression, particularly on intracellular adhesion molecule-1 (ICAM-1) in apolipoprotein-E knockout (apoE(-/-)) mice and human umbilical vein endothelial cells (HUVECs).

Methods and results: ApoE(-/-) mice were treated with sodium hydrosulfide (NaHS) or DL-propargylglycine (PPG); HUVECs were pretreated with NaHS. Compared with control mice, apoE(-/-) mice showed decreased plasma H(2)S level and aortic H(2)S production but increased plasma ICAM-1 and aortic ICAM-1 protein and mRNA. Compared with apoE(-/-) mice, apoE(-/-)+NaHS mice showed increased plasma H(2)S level, but decreased size of atherosclerotic plaque and plasma and aortic ICAM-1 levels, whereas apoE(-/-)+PPG mice showed decreased plasma H(2)S level but enlarged plaque size and increased plasma and aortic ICAM-1 levels. NaHS suppressed ICAM-1 expression in tumor necrosis factor (TNF)-alpha-treated HUVECs. NaHS inhibited IkappaB degradation and NF-kappaB nuclear translocation in HUVECs treated with TNF-alpha.

Conclusions: The vascular CSE/H(2)S pathway was disturbed in apoE(-/-) mice. H(2)S exerted an antiatherogenic effect and inhibited ICAM-1 expression in apoE(-/-) mice. H(2)S inhibited ICAM-1 expression in TNF-alpha-induced HUVECs via the NF-kappaB pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Alkynes / pharmacology
  • Animals
  • Aorta / drug effects*
  • Aorta / metabolism
  • Aorta / ultrastructure
  • Apolipoproteins E / deficiency*
  • Apolipoproteins E / genetics
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control*
  • Body Weight
  • Cardiovascular Agents / pharmacology*
  • Cells, Cultured
  • Cystathionine gamma-Lyase / antagonists & inhibitors
  • Cystathionine gamma-Lyase / genetics
  • Cystathionine gamma-Lyase / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelial Cells / ultrastructure
  • Enzyme Inhibitors / pharmacology
  • Foam Cells / drug effects
  • Foam Cells / metabolism
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • Humans
  • Hydrogen Sulfide / blood
  • Hydrogen Sulfide / metabolism*
  • I-kappa B Proteins / metabolism
  • Intercellular Adhesion Molecule-1 / blood
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Lipids / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • NF-kappa B / metabolism
  • RNA, Messenger / metabolism
  • Sulfides / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Alkynes
  • Apolipoproteins E
  • Cardiovascular Agents
  • Enzyme Inhibitors
  • I-kappa B Proteins
  • Lipids
  • NF-kappa B
  • RNA, Messenger
  • Sulfides
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • propargylglycine
  • Cystathionine gamma-Lyase
  • sodium bisulfide
  • Glycine
  • Hydrogen Sulfide