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 Ϫ/Ϫ ) mice and human umbilical vein endothelial cells (HUVECs). Methods and Results-ApoEϪ/Ϫ mice were treated with sodium hydrosulfide (NaHS) or DL-propargylglycine (PPG); HUVECs were pretreated with NaHS. Compared with control mice, apoE Ϫ/Ϫ 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 Ϫ/Ϫ mice, apoE Ϫ/Ϫ ϩNaHS mice showed increased plasma H 2 S level, but decreased size of atherosclerotic plaque and plasma and aortic ICAM-1 levels, whereas apoE Ϫ/Ϫ ϩPPG 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)-␣-treated HUVECs. NaHS inhibited IB degradation and NF-B nuclear translocation in HUVECs treated with TNF-␣. Ⅲapolipoprotein E knockout mice Ⅲ human umbilical vein endothelial cells A therosclerosis is an important underlying pathology of cardiovascular diseases, the leading cause of morbidity and mortality in many countries. Over the past 50 years, numerous studies attempting to explain the complex events leading to atherosclerosis have been undertaken. Nitric oxide and carbon monoxide, which are small gaseous transmitters, freely permeable to membrane, endogenously and enzymatically generated, and have specific functions, are recommended as gasotransmitters. 1 They have been closely implicated in endothelial dysfunction and vascular remodeling in atherosclerotic arteries; researches into the two gasotransmitters have improved the understanding of atherogenesis. [2][3][4][5] However, the mechanisms of atherosclerosis have not been fully elucidated. Conclusions-The

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The mechanisms responsible for the cardioprotective effect of hydrogen sulfide (H(2)S) are unclear. The present study was designed to examine whether H(2)S could regulate hyperhomocysteinemia (HHcy)-induced cardiomyocytic endoplasmic reticulum (ER) stress. A rat model of HHcy was produced, and H9c2 cells (rat embryonic heart-derived cell line) were cultured. The plasma homocysteine was measured by using HPLC. Plasma H(2)S concentration and myocardial H(2)S production were measured with a sulfide-sensitive electrode. Confocal immunofluorescent analysis for cardiomyocytic C/EBP homologous protein (CHOP) was performed. Glucose-regulated protein 78 (GRP78), CHOP, and caspase 12 expressions by myocardial tissues and cleaved caspase 12 and p-eIF2alpha expressions by H9c2 cells were detected with Western blotting. The results showed that methionine overload induced HHcy, resulting in a marked cardiomyocytic ER stress, whereas endogenous production of H(2)S was reduced in rats with HHcy. H(2)S supplementation, however, decreased expressions of ER stress-associated proteins, including GRP78, CHOP, and caspase 12, by myocardial tissues in vivo. The inhibition of endogenous H(2)S production further enhanced cardiomyocytic ER stress, but H(2)S supplementation effectively antagonized the H9c2 cell CHOP, cleaved caspase 12 and p-eIF2alpha expressions induced by Hcy, thapsigargin, or tunicamycin in vitro. The results suggest that H(2)S can attenuate cardiomyocytic ER stress in HHcy-induced cardiomyocytic injury.

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