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

BackgroundLiver X receptors,LXRα（NR1H3）and LXRβ（NR1H2）,are best known as nuclear oxysterol receptors and physiological master regulators of lipid and cholesterol metabolism.LXRαplay 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-α（LXRα）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 LXRαgene knock-out(LXRα^-/-)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 factorα,interleukin-6 and interleukin-1βwere 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 andα-smooth muscle actin（α-SMA）staining,angiogenesis was observed by CD31 immunofluorescence staining,matrix metalloproteinase-9and typeⅠcollagen 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 LXRα^-/-group at 3 days after MI.At 4weeks post-MI,LXRα^-/-MI murine hearts demonstrated significantly increased infarct size,reduced ejection fraction,aggravated left ventricular（LV）chamber dilation,enhanced fibrosis and reduced angiogenesis.In addition,LXRα^-/-mice had increased mortality compared with WT mice.ConclusionsLXRαdeficiency increases mortality,aggravates pathological injury and left ventricular LV remodeling induced by MI.Drugs specifically targeting LXRαmay be promising in the treatment of MI.