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Digoxin reduces atherosclerosis in apolipoprotein E‐deficient mice
Author(s) -
Shi Huairui,
Mao Xiaobo,
Zhong Yucheng,
Liu Yuzhou,
Zhao Xiaoqi,
Yu Kunwu,
Zhu Ruirui,
Wei Yuzhen,
Zhu Jianghao,
Sun Haitao,
Mao Yi,
Zeng Qiutang
Publication year - 2016
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13453
Subject(s) - digoxin , endocrinology , medicine , apolipoprotein b , inflammation , cholesterol , lipid metabolism , pharmacology , high density lipoprotein , heart failure
Background and Purpose Numerous 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 Approach Apolipoprotein E‐deficient mice maintained on a Western‐type diet were administered PBS (control), low‐dose digoxin (1 mg·kg −1 · day −1 ) or high‐dose digoxin (2 mg·kg −1 · day −1 ) via i.p. injection for 12 weeks. Key Results Digoxin 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 Implications Our data demonstrate that digoxin acts as a specific antagonist of retinoid‐related orphan receptor‐γ to decrease atherosclerosis by suppressing lipid levels and IL‐17A‐related inflammatory responses.