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

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• 作者：Xiaoqiang Liu ; Jianshu Gao ; Qiang Xia ; Tianfei Lu ; Fang Wang
• 刊名：Heart and Vessels
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：31
• 期：8
• 页码：1370-1379
• 全文大小：8,570 KB
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Cardiology
  Cardiac Surgery
  Vascular Surgery
  Biomedical Engineering
  Interventional Radiology
  Ultrasound
  
• 出版者：Springer Japan
• ISSN：1615-2573
• 卷排序：31

文摘

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.KeywordsNuclear receptorsMyocardial infarctionHeart failureMortalityApoptosis