Farnesoid-X-receptor Deletion Improves Cardiac Function,Structure And Remodeling Following Myocardial Infarction In Mice

BacgroudThe Farnesoid-X-receptor(FXR)is a recently discovered member of the metabolic nuclear receptor superfamily.FXR is expressed mainly in liver and gastrointestinal tract.It plays an important role in triglyceride,bile acid,cholesterol and glucose metabolism.More importantly,recent study indicate the presence of FXR in vasculature and heart.However,the potential function of FXR in the heart after myocardial infarction remains unknown.ObjectivesTo explore the effect of FXR konckout on post-myocardial infarction(MI)remodeling of the left ventricle(LV).MethodsThe LAD coronary arteries of wild type(WT)and FXR-/-mice were ligated permanently to produce MI followed by serial echocardiographic and histological testing.After one week,the apoptosis of myocardial cells was evaluated by TUNEL.After four weeks,the heart function and heart size were measured by echocardiography(UCG),and TTC staining was used to measure the area of MI in mice.Protein of Cleaved caspase-3 was detected by Western blotting.Myocardial fibrosis was analized by Masson,and the angiogenesis was detected by CD31 immunofluorescence.RNA of Matrix metalloproteinase type-9 and Collagen ? were further evaluated by RT-PCR assay to assess myocardial fibrosis.ResultsThe improvement of left ventricular remodeling was significant as early as 7 days post-MI in the FXR-/-mice,along with myocyte apoptosis reduction within the infarcted zones,promoted angiogenesis,inhibited fibrosis in the FXR-/-group.ConclusionsThese results from the knockout model demonstrate for the first time that deletion of FXR plays a protective role in preserving post-MI cardiac function by reducing fibrosis,chronic apoptosis and promoting angionesis.