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

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.