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Increased mortality and aggravation of heart failure in liver X receptor-α knockout mice after myocardial infarction

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Abstract

Liver X receptors, LXRα (NR1H3) and LXRβ (NR1H2), are best known as nuclear oxysterol receptors and physiological master regulators of lipid and cholesterol metabolism. LXRα play a protective role in acute myocardial ischemia/reperfusion (MI/R) injury, but its role in myocardial infarction (MI) is unknown. The present study was undertaken to determine the effect of LXRα knockout on survival and development of chronic heart failure after MI. Wild-type (WT) and LXRα−/− mice were subjected to MI followed by serial echocardiographic and histological assessments. Greater myocyte apoptosis and inflammation within the infarcted zones were found in LXRα−/− group at 3 days after MI. At 4 weeks post-MI, LXRα−/− MI murine hearts demonstrated significantly increased infarct size, reduced ejection fraction (LXRα−/− 29.4 % versus WT 34.4 %), aggravated left ventricular (LV) chamber dilation, enhanced fibrosis and reduced angiogenesis. In addition, LXRα−/− mice had increased mortality compared with WT mice. LXRα deficiency increases mortality, aggravates pathological injury and LV remodeling induced by MI. Drugs specifically targeting LXRα may be promising in the treatment of MI.

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Acknowledgments

We thank Laboratory of Transplantation and Hepatic Surgery, Ren Ji Hospital. Furthermore, we are grateful for Jiang Zhang and Dawei Li for providing excellent technical assistance.

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    Authors and Affiliations

    1. Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China

      Xiaoqiang Liu & Fang Wang

    2. Department of Cardiology, Yancheng First People’s Hospital, The Fourth Affiliated Hospital of Nantong University, Yancheng, 224006, Jiangsu, People’s Republic of China

      Jianshu Gao

    3. Department of Transplantation and Hepatic Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China

      Qiang Xia & Tianfei Lu

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    1. Xiaoqiang Liu
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    2. Jianshu Gao
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    5. Fang Wang
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    Correspondence to Fang Wang.

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    The authors declare no conflict of interest.

    Ethical approval

    This investigation conforms to the National Institutes of Health Guidelines on the Use of Laboratory Animals, and was approved by the Institute’s Animal Ethics Committee.

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    X. Liu and J. Gao contributed equally to this work.

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    Liu, X., Gao, J., Xia, Q. et al. Increased mortality and aggravation of heart failure in liver X receptor-α knockout mice after myocardial infarction. Heart Vessels 31, 1370–1379 (2016). https://doi.org/10.1007/s00380-015-0781-y

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    • DOI: https://doi.org/10.1007/s00380-015-0781-y

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