Integrative Physiology/Experimental Medicine 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)–treated HUVECs. NaHS inhibited I B degradation and NFB nuclear translocation in HUVECs treated with TNF. 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-induced HUVECs via the NFB pathway. (Arterioscler Thromb Vasc Biol. 2009;29:173-179.)