Liver X receptor agonist treatment attenuates cardiac dysfunction in type 2 diabetic db/db mice

Cardiovascular Diabetology

Ben He¹  Huan Tong¹  Longwei Xu¹  Yichao Zhao¹  Xiaoying Ying¹  Tianbao Yao¹  Ancai Yuan¹  Jun Pu¹  Qing He¹ 

[1] Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China

关键词: Antioxidant;    Insulin resistance;    Diabetic cardiomyopathy;    Liver X receptor;   

Others  :  1118933
DOI  :  10.1186/s12933-014-0149-0

 received in 2014-05-27, accepted in 2014-10-20,  发布年份 2014

【 摘 要 】

Background

Liver X receptor (LXR) plays a critical regulatory role in metabolism and inflammation, and has been demonstrated to be involved in cardiovascular physiology/pathology. In the present study, we investigated the effect of GW3965, a potent LXR agonist, on diabetic cardiomyopathy (DCM) in type 2 diabetic db/db mice.

Methods and Results

Non-diabetic db/+ mice and diabetic db/db mice received either vehicle or LXR agonist GW3965 for 12 weeks. Systemic insulin resistance was evaluated by glucose tolerance test and homeostasis model assessment for insulin resistance. Endpoint cardiac function was assessed by echocardiography and catheterization. Ventricular tissue was collected for histology and gene/protein expression analysis. Untreated db/db diabetic mice exhibited diastolic dysfunction with adverse structural remodeling (including myocardial fibrosis and increased apoptosis). Treatment with GW3965 remarkably attenuated myocardial dysfunction and structural remodeling in diabetic db/db mice. Mechanistically, GW3965 restored Akt phosphorylation and inhibited MAP kinases phosphorylation, and reduced oxidative/nitrative stress and inflammation response in the diabetic myocardium.

Conclusions

Our data demonstrate that GW3965 exerts a cardioprotective effect against DCM by (at least in part) attenuating insulin resistance, modulating Akt and MAP kinases pathways, and reducing oxidative/nitrative stress and inflammatory response. These findings strongly suggest that LXR agonist may have therapeutic potential in treating DCM.

【 授权许可】

   
2014 He et al.; licensee BioMed Central Ltd.

【 图 表 】

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