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
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus
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Alkynes / pharmacology
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Animals
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Aorta / drug effects*
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Aorta / metabolism
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Aorta / ultrastructure
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Apolipoproteins E / deficiency*
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Apolipoproteins E / genetics
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Atherosclerosis / metabolism
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Atherosclerosis / pathology
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Atherosclerosis / prevention & control*
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Body Weight
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Cardiovascular Agents / pharmacology*
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Cells, Cultured
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Cystathionine gamma-Lyase / antagonists & inhibitors
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Cystathionine gamma-Lyase / genetics
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Cystathionine gamma-Lyase / metabolism
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Endothelial Cells / drug effects*
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Endothelial Cells / metabolism
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Endothelial Cells / ultrastructure
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Enzyme Inhibitors / pharmacology
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Foam Cells / drug effects
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Foam Cells / metabolism
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Glycine / analogs & derivatives
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Glycine / pharmacology
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Humans
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Hydrogen Sulfide / blood
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Hydrogen Sulfide / metabolism*
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I-kappa B Proteins / metabolism
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Intercellular Adhesion Molecule-1 / blood
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Intercellular Adhesion Molecule-1 / metabolism*
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Lipids / blood
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / metabolism
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NF-kappa B / metabolism
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RNA, Messenger / metabolism
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Sulfides / pharmacology*
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Alkynes
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Apolipoproteins E
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Cardiovascular Agents
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Enzyme Inhibitors
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I-kappa B Proteins
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Lipids
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NF-kappa B
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RNA, Messenger
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Sulfides
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Tumor Necrosis Factor-alpha
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Intercellular Adhesion Molecule-1
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propargylglycine
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Cystathionine gamma-Lyase
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sodium bisulfide
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Glycine
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Hydrogen Sulfide