Dataset Information

Digoxin reduces atherosclerosis in apolipoprotein E-deficient mice.

ABSTRACT:

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-? to decrease atherosclerosis by suppressing lipid levels and IL-17A-related inflammatory responses.

SUBMITTER: Shi H

PROVIDER: S-EPMC4831306 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Publications

Digoxin reduces atherosclerosis in apolipoprotein E-deficient mice.

Shi Huairui H Mao Xiaobo X Zhong Yucheng Y Liu Yuzhou Y Zhao Xiaoqi X Yu Kunwu K Zhu Ruirui R Wei Yuzhen Y Zhu Jianghao J Sun Haitao H Mao Yi Y Zeng Qiutang Q

British journal of pharmacology 20160311 9

<h4>Background and purpose</h4>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.<h4>Experimental approach</h4>Apolipoprotein E-deficient mice maintained on a Western-type diet were administered PBS (control), low-dose digo ...[more]

PMID: 26879387

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Project description:Fat inflammation may play an important role in comorbidities associated with obesity such as atherosclerosis.To first establish feasibility of fat transplantation, epididymal fat pads were harvested from wild-type C57BL/6J mice and transplanted into leptin-deficient (Lep(ob/ob)) mice. Fat transplantation produced physiological leptin levels and prevented obesity and infertility in Lep(ob/ob) mice. However, the transplanted fat depots were associated with chronically increased macrophage infiltration with characteristics identical to those observed in fat harvested from obese animals. The inflammation in transplanted adipose depots was regulated by the same factors that have been implicated in endogenous fat inflammation such as monocyte chemoattractant protein-1. To determine whether this inflamed adipose depot could affect vascular disease in mice, epididymal fat depots were transplanted into atherosclerosis-prone apolipoprotein E-deficient ApoE(-/-) mice. Plasma from ApoE(-/-) mice receiving fat transplants contained increased leptin, resistin, and monocyte chemoattractant protein-1 compared with plasma from sham-operated ApoE(-/-) mice. Furthermore, mice transplanted with visceral fat developed significantly more atherosclerosis compared with sham-operated animals, whereas transplants with subcutaneous fat did not affect atherosclerosis despite a similar degree of fat inflammation. Treatment of transplanted ApoE(-/-) mice with pioglitazone decreased macrophage content of the transplanted visceral fat pad and reduced plasma monocyte chemoattractant protein-1. Importantly, pioglitazone also reduced atherosclerosis triggered by inflammatory visceral fat but had no protective effect on atherosclerosis in the absence of the visceral fat transplantation.Our results indicate that visceral adipose-related inflammation accelerates atherosclerosis in mice. Drugs such as thiazolidinediones might be a useful strategy to specifically attenuate the vascular disease induced by visceral inflammatory fat.

Dataset Information

Digoxin reduces atherosclerosis in apolipoprotein E-deficient mice.

Background and purpose

Experimental approach

Key results

Conclusions and implications

Publications

Digoxin reduces atherosclerosis in apolipoprotein E-deficient mice.

Similar Datasets

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