Aggravation Of Heart Failure In Liver X Receptor ? Knockout Mice After Myocardial Infarction

BackgroundLiver X receptors,LXR??NR1H3?and LXR??NR1H2?,are best known as nuclear oxysterol receptors and physiological master regulators of lipid and cholesterol metabolism.LXR?play a protective role in acute myocardial ischemia/reperfusion?MI/R?injury,but its role in myocardial infarction?MI?is unknown.ObjectiveThe present study was undertaken to explore the effect of liver X receptor-??LXR??on chronic heart failure after myocardial infarction?MI?in mice.MethodsThe MI model was established by ligation of left anterior descending coronary artery in wild type?WT?mice and LXR?gene knock-out(LXR?^-/-)mice.Third day after MI,cleaved caspase-3 and p-AKT was detected by Western blot,apoptosis of cardiac muscle cells was evaluated by terminal dUTP nick end labling?TUNEL?staining,and expressions of proinflammatory cytokines tumor necrosis factor?,interleukin-6 and interleukin-1?were detected by quantitative real-time polymerase chain reaction?qRT-PCR?.Fourth week after MI,left ventricular function was assessed with ultrasonic echocardiography,myocardial infarct size was evaluated by 2,3,5-triphenyltetrazolium chloride?TTC?staining,myocardial fibrosis was observed by using Masson trichrome staining and?-smooth muscle actin??-SMA?staining,angiogenesis was observed by CD31 immunofluorescence staining,matrix metalloproteinase-9and type?collagen were detected by qRT-PCR to further assess myocardial fibrosis.Results Compared with WT mice,greater myocyte apoptosis and inflammation within the infarcted zones were found in LXR?^-/-group at 3 days after MI.At 4weeks post-MI,LXR?^-/-MI murine hearts demonstrated significantly increased infarct size,reduced ejection fraction,aggravated left ventricular?LV?chamber dilation,enhanced fibrosis and reduced angiogenesis.In addition,LXR?^-/-mice had increased mortality compared with WT mice.ConclusionsLXR?deficiency increases mortality,aggravates pathological injury and left ventricular LV remodeling induced by MI.Drugs specifically targeting LXR?may be promising in the treatment of MI.