Hydrogen sulfide inhibits the development of atherosclerosis with suppressing CX3CR1 and CX3CL1 expression.
Hydrogen sulfide inhibits the development of atherosclerosis with suppressing CX3CR1 and CX3CL1 expression.
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硫化氢通过抑制 CX3CR1 和 CX3CL1 表达来抑制动脉粥样硬化的发展
DOI：
10.1371/journal.pone.0041147
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Zhang H;Guo C;Wu D;Zhang A;Gu T;Wang L;Wang C
硫化氢作为一种新的气体介质，在动脉粥样硬化的形成中起着重要作用。然而，H2S影响动脉粥样硬化的确切机制仍不清楚。因此，本研究旨在研究H2S在动脉粥样硬化中的潜在作用以及巨噬细胞中趋化因子（CCL 2，CCL 5和CX 3CL 1）和趋化因子受体（CCR 2，CCR 5和CX 3CR 1）的潜在机制。将小鼠巨噬细胞系RAW 264.7或小鼠腹膜巨噬细胞与盐水或NaHS（50 μM、100 μM、200 μM）（H2S供体）预孵育，然后用干扰素-γ（IFN-γ）或脂多糖（LPS）刺激。结果发现，NaHS剂量依赖性地抑制IFN-γ或LPS诱导的巨噬细胞中CX 3CR 1和CX 3CL 1的表达，以及CX 3CR 1介导的趋化性。过表达胱硫醚γ-裂解酶（CSE，一种催化H2S生物合成的酶）导致刺激的巨噬细胞中CX 3CR 1和CX 3CL 1表达以及CX 3CR 1介导的趋化性显著降低。H2S对CX 3CR 1和CX 3CL 1表达的抑制作用是通过调节增殖物激活受体-γ（PPAR-γ）和NF-κB途径介导的。此外，雄性apoE−/−小鼠喂食高脂肪饮食，然后随机给予NaHS（1 mg/kg，i. p.，每日）或DL-炔丙基甘氨酸（PAG，10 mg/kg，i. p.，每日）。NaHS显著抑制主动脉CX 3CR 1和CX 3CL 1的表达，并阻止主动脉斑块的发展。在动脉粥样硬化早期应用NaHS具有更好的抗动脉粥样硬化作用。然而，PAG抑制H2S形成增加了主动脉CX 3CR 1和CX 3CL 1的表达，并加剧了动脉粥样硬化的程度。此外，H2S对体外和体内CCL 2、CCL 5、CCR 2和CCR 5的表达影响极小。总之，这些数据表明，H2S阻碍了脂肪喂养的apoE−/−小鼠动脉粥样硬化的进展，并下调巨噬细胞和病变斑块中CX 3CR 1和CX 3CL 1的表达。
Hydrogen sulfide, as a novel gaseous mediator, has been suggested to play a key role in atherogenesis. However, the precise mechanisms by which H2S affects atherosclerosis remain unclear. Therefore, the present study aimed to investigate the potential role of H2S in atherosclerosis and the underlying mechanism with respect to chemokines (CCL2, CCL5 and CX3CL1) and chemokine receptors (CCR2, CCR5, and CX3CR1) in macrophages. Mouse macrophage cell line RAW 264.7 or mouse peritoneal macrophages were pre-incubated with saline or NaHS (50 µM, 100 µM, 200 µM), an H2S donor, and then stimulated with interferon-γ (IFN-γ) or lipopolysaccharide (LPS). It was found that NaHS dose-dependently inhibited IFN-γ or LPS-induced CX3CR1 and CX3CL1 expression, as well as CX3CR1-mediated chemotaxis in macrophages. Overexpression of cystathionine γ-lyase (CSE), an enzyme that catalyzes H2S biosynthesis resulted in a significant reduction in CX3CR1 and CX3CL1 expression as well as CX3CR1-mediated chemotaxis in stimulated macrophages. The inhibitory effect of H2S on CX3CR1 and CX3CL1 expression was mediated by modulation of proliferators-activated receptor-γ (PPAR-γ) and NF-κB pathway. Furthermore, male apoE−/− mice were fed a high-fat diet and then randomly given NaHS (1 mg/kg, i.p., daily) or DL-propargylglycine (PAG, 10 mg/kg, i.p., daily). NaHS significantly inhibited aortic CX3CR1 and CX3CL1 expression and impeded aortic plaque development. NaHS had a better anti-atherogenic benefit when it was applied at the early stage of atherosclerosis. However, inhibition of H2S formation by PAG increased aortic CX3CR1 and CX3CL1 expression and exacerbated the extent of atherosclerosis. In addition, H2S had minimal effect on the expression of CCL2, CCL5, CCR2 and CCR5 in vitro and in vivo. In conclusion, these data indicate that H2S hampers the progression of atherosclerosis in fat-fed apoE−/− mice and downregulates CX3CR1 and CX3CL1 expression on macrophages and in lesion plaques.
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影响因子：
3.5
作者：
Wan Y;Evans RM
通讯作者：
Evans RM
影响因子：
37.8
作者：
Combadière, C;Potteaux, S;Mallat, Z
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影响因子：
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作者：
Oh, Gi-Su;Pae, Hyun-Ock;Chung, Hun-Taeg
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4.7
作者：
Hu, Li-Fang;Wong, Peter T. -H.;Bian, Jin-Song
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影响因子：
4.8
作者：
Kimura, Y;Kimura, H
通讯作者：
Kimura, H