title: Increased mortality and aggravation of heart failure in liver X receptor-α knockout mice after myocardial infarction.
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.
authors.affiliation: Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People's Republic of China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Yancheng First People's Hospital, The Fourth Affiliated Hospital of Nantong University, Yancheng, 224006, Jiangsu, People's Republic of China.
authors.forename: Jianshu
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Transplantation and Hepatic Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Department of Transplantation and Hepatic Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People's Republic of China.
authors.forename: Tianfei
authors.initials: T
authors.lastname: Lu
authors.affiliation: Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People's Republic of China. onlyfang1@163.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D004452:Echocardiography; D005355:Fibrosis; D006333:Heart Failure / Q000209:etiology*; D006801:Humans; D000071518:Liver X Receptors / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000150:complications* / Q000401:mortality / Q000601:surgery; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging; D020257:Ventricular Remodeling
chemical_list: D000071518:Liver X Receptors
keywords: Apoptosis; Heart failure; Mortality; Myocardial infarction; Nuclear receptors