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 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

Vitamin D Up-regulates Glucose Transporter 4 (GLUT4) Translocation and Glucose Utilization Mediated by Cystathionine-γ-lyase (CSE) Activation and H2S Formation in 3T3L1 Adipocytes

“…H 2 S is produced in vivo from L-cysteine by the action of two main enzymes, CSE and cystathionine ␤-synthase (5-7). Exogenous H 2 S supplementation reduces blood pressure, decreases atherosclerotic plaque size compared with those of controls in apolipoprotein E knock-out mice, and prevents progression of diabetic nephropathy in spontaneously hypertensive rats and endothelial dysfunction in diabetic rats (22,23). Several studies demonstrate that H 2 S is an antioxidant that regenerates GSH and lowers oxidative stress (5)(6)(7)11).…”

“…Vitamin D may upregulate insulin receptors and activate peroxisome proliferatoractivated receptor ␥ expression (28). Vitamin D may increase the synthesis of calbindin, which can alter calcium-dependent insulin secretion by pancreatic ␤-cells (22). Vitamin D can also affect IL-12 secretion via inhibition of NF-B in macrophages and dendritic cells, as well as inhibition of proinflammatory cytokine secretion by modulation of monocyte/macrophage and preadipocyte differentiation (1, 28 -31).…”

The vasorelaxing effect of hydrogen sulfide on isolated rat aortic rings versus pulmonary artery rings

“…H 2 S plays an important role in the regulation of systemic and pulmonary circulation [25][26][27][28][29][30] . Olson et al showed that in rat pulmonary arteries, NaHS produced a transit constriction followed by relaxation for 20 to 30 min, which was then followed by a second constriction [5] .…”

Hydrogen Sulfide and Endothelial Dysfunction: Relationship with Nitric Oxide

“…CSE expression and H 2 S production were significantly decreased during the development of balloon injury-induced neointimal hyperplasia in the rat carotid artery, and that exogenous H 2 S significantly reduced neointimal lesion formation [158]. Treatment of apoE-KO mice with NaHS decreased, and with PPG increased, atherosclerotic lesion size [159]. NaHS (100 µmol/L for 12 hrs) inhibited ICAM-1 expression in TNF-alpha-induced HUVECs via the NF-kB pathway [159].…”

“…Treatment of apoE-KO mice with NaHS decreased, and with PPG increased, atherosclerotic lesion size [159]. NaHS (100 µmol/L for 12 hrs) inhibited ICAM-1 expression in TNF-alpha-induced HUVECs via the NF-kB pathway [159]. Moreover, NaHS administration concentration-dependently (50-200 µM) reduced CX3CR1 and CX3CL1 expression in mouse peritoneal macrophages as well as CX3CR1-mediated chemotaxis [160].…”