Digoxin reduces atherosclerosis in apolipoprotein E-deficient mice

作者：Shi, Huairui; Mao, Xiaobo; Zhong, Yucheng; Liu, Yuzhou; Zhao, Xiaoqi; Yu, Kunwu; Zhu, Ruirui; Wei, Yuzhen; Zhu, Jianghao; Sun, Haitao; Mao, Yi; Zeng, Qiutang^*

来源：British Journal of Pharmacology, 2016, 173(9): 1517-1528.

DOI：10.1111/bph.13453

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Background and PurposeNumerous in vitro studies have suggested that digoxin suppresses inflammation and alters lipid metabolism. However, the effect of dioxin on atherosclerosis is poorly understood. The present study was conducted to determine whether digoxin affects the development of atherosclerosis in a murine model of atherosclerotic disease. @@@ Experimental ApproachApolipoprotein E-deficient mice maintained on a Western-type diet were administered PBS (control), low-dose digoxin (1mgkg(-1) day(-1)) or high-dose digoxin (2mgkg(-1) day(-1)) via i.p. injection for 12weeks. @@@ Key ResultsDigoxin dose-dependently reduced atherosclerotic lesion formation and plasma lipid levels (reductions of 41% in total cholesterol, 54% in triglycerides and 20% in low-density lipoprotein cholesterol in the high-dose digoxin-treated group). Moreover, treatment with digoxin markedly attenuated IL-17A expression and IL-17A-related inflammatory responses and increased the abundance of regulatory T cells (Tregs). @@@ Conclusions and ImplicationsOur data demonstrate that digoxin acts as a specific antagonist of retinoid-related orphan receptor- to decrease atherosclerosis by suppressing lipid levels and IL-17A-related inflammatory responses.

• 出版日期2016-5
• 单位华中科技大学