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

Abstract

Objective-We explored the effect of hydrogen sulfide (H 2S) 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 2S level and aortic H 2S production but increased plasma ICAM-1 and aortic ICAM-1 protein and mRNA. Compared with apoE -/- mice, apoE -/-+NaHS mice showed increased plasma H 2S level, but decreased size of atherosclerotic plaque and plasma and aortic ICAM-1 levels, whereas apoE -/-+PPG mice showed decreased plasma H 2S level but enlarged plaque size and increased plasma and aortic ICAM-1 levels. NaHS suppressed ICAM-1 expression in tumor necrosis factor (TNF)-α-treated HUVECs. NaHS inhibited IκB degradation and NF-κB nuclear translocation in HUVECs treated with TNF-α. Conclusions-The vascular CSE/H 2S pathway was disturbed in apoE -/- mice. H 2S exerted an antiatherogenic effect and inhibited ICAM-1 expression in apoE -/- mice. H 2S inhibited ICAM-1 expression in TNF-α-induced HUVECs via the NF-κB pathway. © 2009 American Heart Association, Inc.