Role of Hydrogen Sulfide in the Development of Atherosclerotic Lesions in Apolipoprotein E Knockout Mice
Role of Hydrogen Sulfide in the Development of Atherosclerotic Lesions in Apolipoprotein E Knockout Mice
复制标题
硫化氢在载脂蛋白 E 敲除小鼠动脉粥样硬化病变发展中的作用
DOI：
10.1161/atvbaha.108.179333
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发表时间：
2009-02-01
影响因子：
8.7
通讯作者：
Du, Junbao
中科院分区：
文献类型：
--
作者：
Wang, Yanfei;Zhao, Xia;Du, Junbao
目的：探讨硫化氢(H_2S)对载脂蛋白E基因敲除小鼠(apoE(-/-))和人脐静脉内皮细胞(HUVECs)动脉粥样硬化进展的影响，尤其是对细胞间黏附分子-1(ICAM-1)的影响。方法和结果：ApoE(-/-)小鼠给予硫化钠(NaHS)或DL-丙叉甘氨酸(PPG)处理；与对照组相比，apoE(-/-)小鼠血浆H_2S水平和主动脉H_2S生成量降低，而血浆ICAM-1和主动脉ICAM-1蛋白和mRNA水平升高。与apoE(-/-)小鼠相比，apoE(-/-)+NAHS组小鼠血浆H_2S水平升高，而动脉粥样硬化斑块大小、血浆和主动脉ICAM-1水平降低，而apoE(-/-)+PPG组小鼠血浆H_2S水平降低，斑块扩大，血浆和主动脉ICAM-1水平升高。NaHS抑制肿瘤坏死因子α诱导的人脐静脉内皮细胞ICAM-1的表达。NaHS抑制肿瘤坏死因子α诱导的人脐静脉内皮细胞I-kappa B降解和核因子-kappaB核转位。结论：apoE(-/-)小鼠血管CSE/H 2S通路发生紊乱。硫化氢具有抗动脉粥样硬化作用，并抑制载脂蛋白E(-/-)小鼠ICAM-1的表达。硫化氢通过核因子-kappa B途径抑制肿瘤坏死因子-α诱导的人脐静脉内皮细胞ICAM-1表达。(动脉血栓血管生物)2009；29：173-179。)
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)-alpha-treated HUVECs. NaHS inhibited I kappa B degradation and NF-kappa B nuclear translocation in HUVECs treated with TNF-alpha.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-alpha-induced HUVECs via the NF-kappa B pathway. (Arterioscler Thromb Vasc Biol. 2009; 29: 173-179.)