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作者

Guohua Song Chuanlong Zong Zhaoqiang Zhang Yang Yu Shutong Yao Peng Jiao Hua Tian Lei Zhai Hui Zhao Shuyan Tian Xiangjian Zhang Yun Wu Xuejun Sun Shucun Qin

作者单位

Heart Center of TaiShan Medical University, Tai'an 271000, China Department of Diving Medicine, Second Military Medical University, Shanghai, China a Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, TaiShan Medical University, Tai'an 271000, China College of Basic Medical Sciences, TaiShan Medical University, Tai'an 271000, China Hebei Collaborative Innovation Center for Cardiocerebrovascular Disease and Hebei Key Laboratory of Vascular Homeostasis, Shijiazhuang 050000, China

刊名

Free Radic Biol Med.

年份

2015

卷号

Vol.87

页码

58-68

ISSN

0891-5849

关键词

Endoplasmic reticulum stress Hydrogen Macrophage apoptosis NF-E2-related factor-2 Plaque stability

摘要

OBJECTIVE: Hydrogen (H2) attenuates the development of atherosclerosis in mouse models. We aimed to examine the effects of H2 on atherosclerotic plaque stability. METHODS: Low-density lipoprotein receptor knockout (LDLR-/-) mice fed an atherogenic-diet were dosed daily with H2 and/or simvastatin. In vitro studies were carried out in oxidized-LDL (ox-LDL)-stimulated macrophage-derived foam cell model treated with or without H2. KEY RESULTS: H2 or simvastatin significantly enhanced plaque stabilit...更多

OBJECTIVE: Hydrogen (H2) attenuates the development of atherosclerosis in mouse models. We aimed to examine the effects of H2 on atherosclerotic plaque stability. METHODS: Low-density lipoprotein receptor knockout (LDLR-/-) mice fed an atherogenic-diet were dosed daily with H2 and/or simvastatin. In vitro studies were carried out in oxidized-LDL (ox-LDL)-stimulated macrophage-derived foam cell model treated with or without H2. KEY RESULTS: H2 or simvastatin significantly enhanced plaque stability by increasing levels of collagen and smooth muscle cells, as well as reducing macrophage and lipid levels in plaques. The decreased numbers of dendritic cells and increased numbers of regulatory T cells in plaques further supported the stabilizing effect of H2 or simvastatin. Moreover, H2 treatment decreased serum ox-LDL level and apoptosis in plaques with concomitant inhibition of endoplasmic reticulum stress (ERS) and reduction of ROS accumulation in the aorta. In vitro, like ERS inhibitor 4-phenylbutyric acid, H2 inhibited ox-LDL- or tunicamycin (an ERS inducer)-induced ERS response and cell apoptosis. In addition, like ROS scavenger N-acetyl-cysteine, H2 inhibited ox-LDL- or Cu2+ (an ROS inducer)-induced reduction in cell viability and increase in cellular ROS. Also, H2 increased Nrf2 (NF-E2-related factor-2, an important factor in antioxidant signaling) activation and Nrf2 siRNA abolished the protective effect of H2 on ox-LDL-induced cellular ROS production. CONCLUSIONS: The inhibitory effects of H2 on the apoptosis of macrophage-derived foam cells, which take effect by suppressing the activation of ERS pathway and by activating Nrf2 antioxidant pathway, might lead to an improvement in atherosclerotic plaque stability.收起

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