title: Digoxin reduces atherosclerosis in apolipoprotein E-deficient mice.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Huairui
authors.initials: H
authors.lastname: Shi
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Mao
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yucheng
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yuzhou
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Kunwu
authors.initials: K
authors.lastname: Yu
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Zhu
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Wei
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jianghao
authors.initials: J
authors.lastname: Zhu
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Sun
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Mao
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Qiutang
authors.initials: Q
authors.lastname: Zeng
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D004077:Digoxin / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000037:antagonists & inhibitors
chemical_list: D001057:Apolipoproteins E; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D004077:Digoxin