Role of Hydrogen Sulfide in the Development of Atherosclerotic Lesions in Apolipoprotein E Knockout Mice

Objective-We explored the effect of hydrogen sulfide (H2S) 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 H2S level and aortic H2S production but increased plasma ICAM-1 and aortic ICAM-1 protein and mRNA. Compared with apoE(-/-) mice, apoE(-/-) +NaHS mice showed increased plasma H2S level, but decreased size of atherosclerotic plaque and plasma and aortic ICAM-1 levels, whereas apoE(-/-) +PPG mice showed decreased plasma H2S 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 I kappa B degradation and NF-kappa B nuclear translocation in HUVECs treated with TNF-alpha. Conclusions-The vascular CSE/H2S pathway was disturbed in apoE(-/-) mice. H2S exerted an antiatherogenic effect and inhibited ICAM-1 expression in apoE(-/-) mice. H2S inhibited ICAM-1 expression in TNF-alpha-induced HUVECs via the NF-kappa B pathway. (Arterioscler Thromb Vasc Biol. 2009; 29: 173-179.)